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Published in: Cancer and Metastasis Reviews 1/2024

30-09-2023 | Review

Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance

Authors: Deepti Singh, Hifzur R. Siddique

Published in: Cancer and Metastasis Reviews | Issue 1/2024

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Abstract

Cancer cells undergo phenotypic switching (cancer cell plasticity) in response to microenvironmental cues, including exposure to therapy/treatment. Phenotypic plasticity enables the cancer cells to acquire more mesenchymal traits promoting cancer cells’ growth, survival, therapy resistance, and disease recurrence. A significant program in cancer cell plasticity is epithelial-to-mesenchymal transition (EMT), wherein a comprehensive reprogramming of gene expression occurs to facilitate the translational shift from epithelial-to-mesenchymal phenotypes resulting in increased invasiveness and metastasis. In addition, EMT plays a pivotal role in facilitating cancer cells’ escape from the body’s immune system using several mechanisms, such as the downregulation of major histocompatibility complex–mediated antigen presentation, upregulation of immune checkpoint molecules, and recruitment of immune-suppressive cells. Cancer cells’ ability to undergo phenotypic switching and EMT-driven immune escape presents a formidable obstacle in cancer management, highlighting the need to unravel the intricate mechanisms underlying these processes and develop novel therapeutic strategies. This article discusses the role of EMT in promoting immune evasion and therapy resistance. We also discuss the ongoing research on developing therapeutic approaches targeting intrinsic and induced cell plasticity within the immune suppressive microenvironment. We believe this review article will update the current research status and equip researchers, clinicians, and other healthcare professionals with valuable insights enhancing their existing knowledge and shedding light on promising directions for future cancer research. This will facilitate the development of innovative strategies for managing therapy-resistant cancers and improving patient outcomes.
Literature
1.
go back to reference Paksa, A., & Rajagopal, J. (2017). The epigenetic basis of cellular plasticity. Current Opinion In Cell Biology, 49, 116–122.PubMed Paksa, A., & Rajagopal, J. (2017). The epigenetic basis of cellular plasticity. Current Opinion In Cell Biology, 49, 116–122.PubMed
2.
go back to reference Quintanal-Villalonga, A., Taniguchi, H., Zhan, Y. A., Hasan, M. M., Chavan, S. S., Meng, F., Uddin, F., Allaj, V., Manoj, P., Shah, N. S., Chan, J. M., Ciampricotti, M., Chow, A., Offin, M., Ray-Kirton, J., Egger, J. D., Bhanot, U. K., Linkov, I., Asher, M., et al. (2021). Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation. Journal of Hematology & Oncology, 14(1), 170. Quintanal-Villalonga, A., Taniguchi, H., Zhan, Y. A., Hasan, M. M., Chavan, S. S., Meng, F., Uddin, F., Allaj, V., Manoj, P., Shah, N. S., Chan, J. M., Ciampricotti, M., Chow, A., Offin, M., Ray-Kirton, J., Egger, J. D., Bhanot, U. K., Linkov, I., Asher, M., et al. (2021). Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation. Journal of Hematology & Oncology, 14(1), 170.
3.
go back to reference Saha, S., Mukherjee, S., Khan, P., Kajal, K., Mazumdar, M., Manna, A., Mukherjee, S., De, S., Jana, D., Sarkar, D. K., & Das, T. (2016). Aspirin suppresses the acquisition of chemoresistance in breast cancer by disrupting an NFκB-IL6 signaling axis responsible for the generation of cancer stem cells. Cancer Research, 76(7), 2000–2012.PubMed Saha, S., Mukherjee, S., Khan, P., Kajal, K., Mazumdar, M., Manna, A., Mukherjee, S., De, S., Jana, D., Sarkar, D. K., & Das, T. (2016). Aspirin suppresses the acquisition of chemoresistance in breast cancer by disrupting an NFκB-IL6 signaling axis responsible for the generation of cancer stem cells. Cancer Research, 76(7), 2000–2012.PubMed
4.
go back to reference Francescangeli, F., Contavalli, P., De Angelis, M. L., Careccia, S., Signore, M., Haas, T. L., Salaris, F., Baiocchi, M., Boe, A., Giuliani, A., Tcheremenskaia, O., Pagliuca, A., Guardiola, O., Minchiotti, G., Colace, L., Ciardi, A., D'Andrea, V., La Torre, F., Medema, J., et al. (2020). A pre-existing population of ZEB2+ quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer. Journal of Experimental & Clinical Cancer Research, 39(1), 2. Francescangeli, F., Contavalli, P., De Angelis, M. L., Careccia, S., Signore, M., Haas, T. L., Salaris, F., Baiocchi, M., Boe, A., Giuliani, A., Tcheremenskaia, O., Pagliuca, A., Guardiola, O., Minchiotti, G., Colace, L., Ciardi, A., D'Andrea, V., La Torre, F., Medema, J., et al. (2020). A pre-existing population of ZEB2+ quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer. Journal of Experimental & Clinical Cancer Research, 39(1), 2.
5.
go back to reference Boumahdi, S., & de Sauvage, F. J. (2020). The great escape: tumour cell plasticity in resistance to targeted therapy. Nature reviews. Drug Discovery, 19(1), 39–56.PubMed Boumahdi, S., & de Sauvage, F. J. (2020). The great escape: tumour cell plasticity in resistance to targeted therapy. Nature reviews. Drug Discovery, 19(1), 39–56.PubMed
6.
go back to reference Shaffer, S. M., Dunagin, M. C., Torborg, S. R., Torre, E. A., Emert, B., Krepler, C., Beqiri, M., Sproesser, K., Brafford, P. A., Xiao, M., Eggan, E., Anastopoulos, I. N., Vargas-Garcia, C. A., Singh, A., Nathanson, K. L., Herlyn, M., & Raj, A. (2017). Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance. Nature, 546(7658), 431–435.PubMedPubMedCentral Shaffer, S. M., Dunagin, M. C., Torborg, S. R., Torre, E. A., Emert, B., Krepler, C., Beqiri, M., Sproesser, K., Brafford, P. A., Xiao, M., Eggan, E., Anastopoulos, I. N., Vargas-Garcia, C. A., Singh, A., Nathanson, K. L., Herlyn, M., & Raj, A. (2017). Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance. Nature, 546(7658), 431–435.PubMedPubMedCentral
7.
go back to reference Qin, S., Jiang, J., Lu, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020). The emerging role of tumor cell plasticity in modifying therapeutic response. Signal Transduction And Targeted Therapy, 5(1), 228.PubMedPubMedCentral Qin, S., Jiang, J., Lu, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020). The emerging role of tumor cell plasticity in modifying therapeutic response. Signal Transduction And Targeted Therapy, 5(1), 228.PubMedPubMedCentral
8.
go back to reference Cabanos, H. F., & Hata, A. N. (2021). Emerging insights into targeted therapy-tolerant persister cells in cancer. Cancers, 13(11), 2666.PubMedPubMedCentral Cabanos, H. F., & Hata, A. N. (2021). Emerging insights into targeted therapy-tolerant persister cells in cancer. Cancers, 13(11), 2666.PubMedPubMedCentral
9.
go back to reference Xue, Y., Martelotto, L., Baslan, T., Vides, A., Solomon, M., Mai, T. T., Chaudhary, N., Riely, G. J., Li, B. T., Scott, K., Cechhi, F., Stierner, U., Chadalavada, K., de Stanchina, E., Schwartz, S., Hembrough, T., Nanjangud, G., Berger, M. F., Nilsson, J., et al. (2017). An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer. Nature Medicine, 23(8), 929–937.PubMedPubMedCentral Xue, Y., Martelotto, L., Baslan, T., Vides, A., Solomon, M., Mai, T. T., Chaudhary, N., Riely, G. J., Li, B. T., Scott, K., Cechhi, F., Stierner, U., Chadalavada, K., de Stanchina, E., Schwartz, S., Hembrough, T., Nanjangud, G., Berger, M. F., Nilsson, J., et al. (2017). An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer. Nature Medicine, 23(8), 929–937.PubMedPubMedCentral
10.
go back to reference Singh, D., Khan, M. A., & Siddique, H. R. (2022). Role of p53-miRNAs circuitry in immune surveillance and cancer development: A potential avenue for therapeutic intervention. Seminars in Cell & Developmental Biology, 124, 15–25. Singh, D., Khan, M. A., & Siddique, H. R. (2022). Role of p53-miRNAs circuitry in immune surveillance and cancer development: A potential avenue for therapeutic intervention. Seminars in Cell & Developmental Biology, 124, 15–25.
11.
go back to reference Wei, S. C., Duffy, C. R., & Allison, J. P. (2018). Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discovery, 8(9), 1069–1086.PubMed Wei, S. C., Duffy, C. R., & Allison, J. P. (2018). Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discovery, 8(9), 1069–1086.PubMed
12.
go back to reference Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017). Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell, 168(4), 707–723.PubMedPubMedCentral Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017). Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell, 168(4), 707–723.PubMedPubMedCentral
13.
go back to reference Shibue, T., & Weinberg, R. A. (2017). EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nature reviews. Clinical Oncology, 14(10), 611–629.PubMedPubMedCentral Shibue, T., & Weinberg, R. A. (2017). EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nature reviews. Clinical Oncology, 14(10), 611–629.PubMedPubMedCentral
14.
go back to reference Zhu, X., Chen, L., Liu, L., & Niu, X. (2019). EMT-mediated acquired EGFR-TKI resistance in NSCLC: Mechanisms and strategies. Frontiers In Oncology, 9, 1044.PubMedPubMedCentral Zhu, X., Chen, L., Liu, L., & Niu, X. (2019). EMT-mediated acquired EGFR-TKI resistance in NSCLC: Mechanisms and strategies. Frontiers In Oncology, 9, 1044.PubMedPubMedCentral
15.
go back to reference Hass, R., von der Ohe, J., & Ungefroren, H. (2020). The intimate relationship among EMT, MET, and TME: A t(ransdifferentiation) e(nhancing) m(ix) to be exploited for therapeutic purposes. Cancers, 12(12), 3674.PubMedPubMedCentral Hass, R., von der Ohe, J., & Ungefroren, H. (2020). The intimate relationship among EMT, MET, and TME: A t(ransdifferentiation) e(nhancing) m(ix) to be exploited for therapeutic purposes. Cancers, 12(12), 3674.PubMedPubMedCentral
16.
go back to reference De Angelis, M. L., Francescangeli, F., & Zeuner, A. (2019). Breast cancer stem cells as drivers of tumor chemoresistance, dormancy and relapse: New challenges and therapeutic opportunities. Cancers, 11(10), 1569.PubMedPubMedCentral De Angelis, M. L., Francescangeli, F., & Zeuner, A. (2019). Breast cancer stem cells as drivers of tumor chemoresistance, dormancy and relapse: New challenges and therapeutic opportunities. Cancers, 11(10), 1569.PubMedPubMedCentral
17.
go back to reference Culig, Z. (2019). Epithelial mesenchymal transition and resistance in endocrine-related cancers. Biochimica et biophysica acta. Molecular. Cell Research, 1866(9), 1368–1375. Culig, Z. (2019). Epithelial mesenchymal transition and resistance in endocrine-related cancers. Biochimica et biophysica acta. Molecular. Cell Research, 1866(9), 1368–1375.
18.
go back to reference Paulitschke, V., Eichhoff, O., Gerner, C., Paulitschke, P., Bileck, A., Mohr, T., Cheng, P. F., Leitner, A., Guenova, E., Saulite, I., Freiberger, S. N., Irmisch, A., Knapp, B., Zila, N., Chatziisaak, T. P., Stephan, J., Mangana, J., Kunstfeld, R., Pehamberger, H., et al. (2019). Proteomic identification of a marker signature for MAPKi resistance in melanoma. The EMBO Journal, 38(15), e95874.PubMedPubMedCentral Paulitschke, V., Eichhoff, O., Gerner, C., Paulitschke, P., Bileck, A., Mohr, T., Cheng, P. F., Leitner, A., Guenova, E., Saulite, I., Freiberger, S. N., Irmisch, A., Knapp, B., Zila, N., Chatziisaak, T. P., Stephan, J., Mangana, J., Kunstfeld, R., Pehamberger, H., et al. (2019). Proteomic identification of a marker signature for MAPKi resistance in melanoma. The EMBO Journal, 38(15), e95874.PubMedPubMedCentral
19.
go back to reference Farmer, P., Bonnefoi, H., Anderle, P., Cameron, D., Wirapati, P., Becette, V., André, S., Piccart, M., Campone, M., Brain, E., Macgrogan, G., Petit, T., Jassem, J., Bibeau, F., Blot, E., Bogaerts, J., Aguet, M., Bergh, J., Iggo, R., & Delorenzi, M. (2009). A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nature Medicine, 15(1), 68–74.PubMed Farmer, P., Bonnefoi, H., Anderle, P., Cameron, D., Wirapati, P., Becette, V., André, S., Piccart, M., Campone, M., Brain, E., Macgrogan, G., Petit, T., Jassem, J., Bibeau, F., Blot, E., Bogaerts, J., Aguet, M., Bergh, J., Iggo, R., & Delorenzi, M. (2009). A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nature Medicine, 15(1), 68–74.PubMed
20.
go back to reference Luke, J. J., Bao, R., Sweis, R. F., Spranger, S., & Gajewski, T. F. (2019). WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clinical Cancer Research, 25(10), 3074–3083.PubMedPubMedCentral Luke, J. J., Bao, R., Sweis, R. F., Spranger, S., & Gajewski, T. F. (2019). WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clinical Cancer Research, 25(10), 3074–3083.PubMedPubMedCentral
21.
go back to reference Ruiz de Galarreta, M., Bresnahan, E., Molina-Sánchez, P., Lindblad, K. E., Maier, B., Sia, D., Puigvehi, M., Miguela, V., Casanova-Acebes, M., Dhainaut, M., Villacorta-Martin, C., Singhi, A. D., Moghe, A., von Felden, J., Tal Grinspan, L., Wang, S., Kamphorst, A. O., Monga, S. P., Brown, B. D., et al. (2019). β-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discovery, 9(8), 1124–1141.PubMed Ruiz de Galarreta, M., Bresnahan, E., Molina-Sánchez, P., Lindblad, K. E., Maier, B., Sia, D., Puigvehi, M., Miguela, V., Casanova-Acebes, M., Dhainaut, M., Villacorta-Martin, C., Singhi, A. D., Moghe, A., von Felden, J., Tal Grinspan, L., Wang, S., Kamphorst, A. O., Monga, S. P., Brown, B. D., et al. (2019). β-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discovery, 9(8), 1124–1141.PubMed
22.
go back to reference Singh, D., Khan, M. A., & Siddique, H. R. (2022). Specific targeting of cancer stem cells by immunotherapy: A possible stratagem to restrain cancer recurrence and metastasis. Biochemical Pharmacology, 198, 114955.PubMed Singh, D., Khan, M. A., & Siddique, H. R. (2022). Specific targeting of cancer stem cells by immunotherapy: A possible stratagem to restrain cancer recurrence and metastasis. Biochemical Pharmacology, 198, 114955.PubMed
23.
go back to reference Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y. H., Byers, L. A., Zhang, X., Yi, X., Dwyer, D., Lin, W., Diao, L., Wang, J., Roybal, J., Patel, M., Ungewiss, C., Peng, D., Antonia, S., Mediavilla-Varela, M., Robertson, G., et al. (2014). Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nature Communications, 5, 5241.PubMed Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y. H., Byers, L. A., Zhang, X., Yi, X., Dwyer, D., Lin, W., Diao, L., Wang, J., Roybal, J., Patel, M., Ungewiss, C., Peng, D., Antonia, S., Mediavilla-Varela, M., Robertson, G., et al. (2014). Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nature Communications, 5, 5241.PubMed
24.
go back to reference Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., Bot, B. M., Morris, J. S., Simon, I. M., Gerster, S., Fessler, E., De Sousa, E., Melo, F., Missiaglia, E., Ramay, H., et al. (2015). The consensus molecular subtypes of colorectal cancer. Nature Medicine, 21(11), 1350–1356.PubMedPubMedCentral Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., Bot, B. M., Morris, J. S., Simon, I. M., Gerster, S., Fessler, E., De Sousa, E., Melo, F., Missiaglia, E., Ramay, H., et al. (2015). The consensus molecular subtypes of colorectal cancer. Nature Medicine, 21(11), 1350–1356.PubMedPubMedCentral
25.
go back to reference Mak, M. P., Tong, P., Diao, L., Cardnell, R. J., Gibbons, D. L., William, W. N., Skoulidis, F., Parra, E. R., Rodriguez-Canales, J., Wistuba, I. I., Heymach, J. V., Weinstein, J. N., Coombes, K. R., Wang, J., & Byers, L. A. (2016). A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune target enrichment following epithelial-to-mesenchymal transition. Clinical Cancer Research, 22(3), 609–620.PubMed Mak, M. P., Tong, P., Diao, L., Cardnell, R. J., Gibbons, D. L., William, W. N., Skoulidis, F., Parra, E. R., Rodriguez-Canales, J., Wistuba, I. I., Heymach, J. V., Weinstein, J. N., Coombes, K. R., Wang, J., & Byers, L. A. (2016). A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune target enrichment following epithelial-to-mesenchymal transition. Clinical Cancer Research, 22(3), 609–620.PubMed
26.
go back to reference Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., Seja, E., Lomeli, S., Kong, X., Kelley, M. C., Sosman, J. A., Johnson, D. B., Ribas, A., & Lo, R. S. (2016). Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell, 165(1), 35–44.PubMedPubMedCentral Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., Seja, E., Lomeli, S., Kong, X., Kelley, M. C., Sosman, J. A., Johnson, D. B., Ribas, A., & Lo, R. S. (2016). Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell, 165(1), 35–44.PubMedPubMedCentral
27.
go back to reference Trujillo, J. A., Luke, J. J., Zha, Y., Segal, J. P., Ritterhouse, L. L., Spranger, S., Matijevich, K., & Gajewski, T. F. (2019). Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma. Journal For Immunotherapy of Cancer, 7(1), 295.PubMedPubMedCentral Trujillo, J. A., Luke, J. J., Zha, Y., Segal, J. P., Ritterhouse, L. L., Spranger, S., Matijevich, K., & Gajewski, T. F. (2019). Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma. Journal For Immunotherapy of Cancer, 7(1), 295.PubMedPubMedCentral
28.
go back to reference Zhan, T., Rindtorff, N., & Boutros, M. (2017). Wnt signaling in cancer. Oncogene, 36(11), 1461–1473.PubMed Zhan, T., Rindtorff, N., & Boutros, M. (2017). Wnt signaling in cancer. Oncogene, 36(11), 1461–1473.PubMed
29.
go back to reference Kudo-Saito, C., Shirako, H., Takeuchi, T., & Kawakami, Y. (2009). Cancer metastasis is accelerated through immunosuppression during SNAIL-induced EMT of cancer cells. Cancer Cell, 15(3), 195–206.PubMed Kudo-Saito, C., Shirako, H., Takeuchi, T., & Kawakami, Y. (2009). Cancer metastasis is accelerated through immunosuppression during SNAIL-induced EMT of cancer cells. Cancer Cell, 15(3), 195–206.PubMed
30.
go back to reference Akalay, I., Janji, B., Hasmim, M., Noman, M. Z., André, F., De Cremoux, P., Bertheau, P., Badoual, C., Vielh, P., Larsen, A. K., Sabbah, M., Tan, T. Z., Keira, J. H., Hung, N. T., Thiery, J. P., Mami-Chouaib, F., & Chouaib, S. (2013). Epithelial-to-mesenchymal transition and autophagy induction in breast carcinoma promote escape from T-cell-mediated lysis. Cancer Research, 73(8), 2418–2427.PubMed Akalay, I., Janji, B., Hasmim, M., Noman, M. Z., André, F., De Cremoux, P., Bertheau, P., Badoual, C., Vielh, P., Larsen, A. K., Sabbah, M., Tan, T. Z., Keira, J. H., Hung, N. T., Thiery, J. P., Mami-Chouaib, F., & Chouaib, S. (2013). Epithelial-to-mesenchymal transition and autophagy induction in breast carcinoma promote escape from T-cell-mediated lysis. Cancer Research, 73(8), 2418–2427.PubMed
31.
go back to reference Fernando, R. I., Litzinger, M., Trono, P., Hamilton, D. H., Schlom, J., & Palena, C. (2010). The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. The Journal of Clinical Investigation, 120(2), 533–544.PubMedPubMedCentral Fernando, R. I., Litzinger, M., Trono, P., Hamilton, D. H., Schlom, J., & Palena, C. (2010). The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. The Journal of Clinical Investigation, 120(2), 533–544.PubMedPubMedCentral
32.
go back to reference Huang, B., Cohen, J. R., Fernando, R. I., Hamilton, D. H., Litzinger, M. T., Hodge, J. W., & Palena, C. (2013). The embryonic transcription factor Brachyury blocks cell cycle progression and mediates tumor resistance to conventional antitumor therapies. Cell Death & Disease, 4(6), e682. Huang, B., Cohen, J. R., Fernando, R. I., Hamilton, D. H., Litzinger, M. T., Hodge, J. W., & Palena, C. (2013). The embryonic transcription factor Brachyury blocks cell cycle progression and mediates tumor resistance to conventional antitumor therapies. Cell Death & Disease, 4(6), e682.
33.
go back to reference Hamilton, D. H., Huang, B., Fernando, R. I., Tsang, K. Y., & Palena, C. (2014). WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition. Cancer Research, 74(9), 2510–2519.PubMedPubMedCentral Hamilton, D. H., Huang, B., Fernando, R. I., Tsang, K. Y., & Palena, C. (2014). WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition. Cancer Research, 74(9), 2510–2519.PubMedPubMedCentral
34.
go back to reference David, J. M., Hamilton, D. H., & Palena, C. (2016). MUC1 upregulation promotes immune resistance in tumor cells undergoing brachyury-mediated epithelial-mesenchymal transition. Oncoimmunology, 5(4), e1117738.PubMedPubMedCentral David, J. M., Hamilton, D. H., & Palena, C. (2016). MUC1 upregulation promotes immune resistance in tumor cells undergoing brachyury-mediated epithelial-mesenchymal transition. Oncoimmunology, 5(4), e1117738.PubMedPubMedCentral
35.
go back to reference Terry, S., Buart, S., Tan, T. Z., Gros, G., Noman, M. Z., Lorens, J. B., Mami-Chouaib, F., Thiery, J. P., & Chouaib, S. (2017). Acquisition of tumor cell phenotypic diversity along the EMT spectrum under hypoxic pressure: Consequences on susceptibility to cell-mediated cytotoxicity. Oncoimmunology, 6(2), e1271858.PubMedPubMedCentral Terry, S., Buart, S., Tan, T. Z., Gros, G., Noman, M. Z., Lorens, J. B., Mami-Chouaib, F., Thiery, J. P., & Chouaib, S. (2017). Acquisition of tumor cell phenotypic diversity along the EMT spectrum under hypoxic pressure: Consequences on susceptibility to cell-mediated cytotoxicity. Oncoimmunology, 6(2), e1271858.PubMedPubMedCentral
36.
go back to reference Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., Miller, M. L., Rekhtman, N., Moreira, A. L., Ibrahim, F., Bruggeman, C., Gasmi, B., Zappasodi, R., Maeda, Y., Sander, C., et al. (2015). Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (New York, N.Y., 348(6230), 124–128.PubMedPubMedCentral Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., Miller, M. L., Rekhtman, N., Moreira, A. L., Ibrahim, F., Bruggeman, C., Gasmi, B., Zappasodi, R., Maeda, Y., Sander, C., et al. (2015). Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (New York, N.Y., 348(6230), 124–128.PubMedPubMedCentral
37.
go back to reference Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., Saco, J., Homet Moreno, B., Mezzadra, R., Chmielowski, B., Ruchalski, K., Shintaku, I. P., Sanchez, P. J., Puig-Saus, C., Cherry, G., et al. (2016). Mutations associated with acquired resistance to PD-1 blockade in melanoma. The New England Journal of Medicine, 375(9), 819–829.PubMedPubMedCentral Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., Saco, J., Homet Moreno, B., Mezzadra, R., Chmielowski, B., Ruchalski, K., Shintaku, I. P., Sanchez, P. J., Puig-Saus, C., Cherry, G., et al. (2016). Mutations associated with acquired resistance to PD-1 blockade in melanoma. The New England Journal of Medicine, 375(9), 819–829.PubMedPubMedCentral
38.
go back to reference Lu, X., Horner, J. W., Paul, E., Shang, X., Troncoso, P., Deng, P., Jiang, S., Chang, Q., Spring, D. J., Sharma, P., Zebala, J. A., Maeda, D. Y., Wang, Y. A., & DePinho, R. A. (2017). Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature, 543(7647), 728–732.PubMedPubMedCentral Lu, X., Horner, J. W., Paul, E., Shang, X., Troncoso, P., Deng, P., Jiang, S., Chang, Q., Spring, D. J., Sharma, P., Zebala, J. A., Maeda, D. Y., Wang, Y. A., & DePinho, R. A. (2017). Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature, 543(7647), 728–732.PubMedPubMedCentral
39.
go back to reference Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., Ali, S. M., Elvin, J. A., Singal, G., Ross, J. S., Fabrizio, D., Szabo, P. M., Chang, H., Sasson, A., Srinivasan, S., et al. (2018). STK11/LKB1 Mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 8(7), 822–835.PubMedPubMedCentral Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., Ali, S. M., Elvin, J. A., Singal, G., Ross, J. S., Fabrizio, D., Szabo, P. M., Chang, H., Sasson, A., Srinivasan, S., et al. (2018). STK11/LKB1 Mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 8(7), 822–835.PubMedPubMedCentral
40.
go back to reference Xu, J. W., Wang, L., Cheng, Y. G., Zhang, G. Y., Hu, S. Y., Zhou, B., & Zhan, H. X. (2018). Immunotherapy for pancreatic cancer: A long and hopeful journey. Cancer Letters, 425, 143–151.PubMed Xu, J. W., Wang, L., Cheng, Y. G., Zhang, G. Y., Hu, S. Y., Zhou, B., & Zhan, H. X. (2018). Immunotherapy for pancreatic cancer: A long and hopeful journey. Cancer Letters, 425, 143–151.PubMed
41.
go back to reference Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel, E. E., III, Koeppen, H., Astarita, J. L., Cubas, R., Jhunjhunwala, S., Banchereau, R., Yang, Y., Guan, Y., Chalouni, C., Ziai, J., Şenbabaoğlu, Y., Santoro, S., Sheinson, D., et al. (2018). TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature, 554(7693), 544–548.PubMedPubMedCentral Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel, E. E., III, Koeppen, H., Astarita, J. L., Cubas, R., Jhunjhunwala, S., Banchereau, R., Yang, Y., Guan, Y., Chalouni, C., Ziai, J., Şenbabaoğlu, Y., Santoro, S., Sheinson, D., et al. (2018). TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature, 554(7693), 544–548.PubMedPubMedCentral
42.
go back to reference Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., Byrom, D., Matarin, J. A., Calon, A., Rivas, E. I., Nebreda, A. R., Riera, A., Attolini, C. S., & Batlle, E. (2018). TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature, 554(7693), 538–543.PubMed Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., Byrom, D., Matarin, J. A., Calon, A., Rivas, E. I., Nebreda, A. R., Riera, A., Attolini, C. S., & Batlle, E. (2018). TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature, 554(7693), 538–543.PubMed
43.
go back to reference Datar, I., & Schalper, K. A. (2016). Epithelial-mesenchymal transition and immune evasion during lung cancer progression: The chicken or the egg? Clinical Cancer Research, 22(14), 3422–3424.PubMedPubMedCentral Datar, I., & Schalper, K. A. (2016). Epithelial-mesenchymal transition and immune evasion during lung cancer progression: The chicken or the egg? Clinical Cancer Research, 22(14), 3422–3424.PubMedPubMedCentral
44.
go back to reference Lou, Y., Diao, L., Cuentas, E. R., Denning, W. L., Chen, L., Fan, Y. H., Byers, L. A., Wang, J., Papadimitrakopoulou, V. A., Behrens, C., Rodriguez, J. C., Hwu, P., Wistuba, I. I., Heymach, J. V., & Gibbons, D. L. (2016). Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma. Clinical Cancer Research, 22(14), 3630–3642.PubMedPubMedCentral Lou, Y., Diao, L., Cuentas, E. R., Denning, W. L., Chen, L., Fan, Y. H., Byers, L. A., Wang, J., Papadimitrakopoulou, V. A., Behrens, C., Rodriguez, J. C., Hwu, P., Wistuba, I. I., Heymach, J. V., & Gibbons, D. L. (2016). Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma. Clinical Cancer Research, 22(14), 3630–3642.PubMedPubMedCentral
45.
go back to reference Hsu, D. S., Wang, H. J., Tai, S. K., Chou, C. H., Hsieh, C. H., Chiu, P. H., Chen, N. J., & Yang, M. H. (2014). Acetylation of SNAIL modulates the cytokinome of cancer cells to enhance the recruitment of macrophages. Cancer Cell, 26(4), 534–548.PubMed Hsu, D. S., Wang, H. J., Tai, S. K., Chou, C. H., Hsieh, C. H., Chiu, P. H., Chen, N. J., & Yang, M. H. (2014). Acetylation of SNAIL modulates the cytokinome of cancer cells to enhance the recruitment of macrophages. Cancer Cell, 26(4), 534–548.PubMed
46.
go back to reference Dongre, A., Rashidian, M., Eaton, E. N., Reinhardt, F., Thiru, P., Zagorulya, M., Nepal, S., Banaz, T., Martner, A., Spranger, S., & Weinberg, R. A. (2021). Direct and indirect regulators of epithelial-mesenchymal transition-mediated immunosuppression in breast carcinomas. Cancer Discovery, 11(5), 1286–1305.PubMed Dongre, A., Rashidian, M., Eaton, E. N., Reinhardt, F., Thiru, P., Zagorulya, M., Nepal, S., Banaz, T., Martner, A., Spranger, S., & Weinberg, R. A. (2021). Direct and indirect regulators of epithelial-mesenchymal transition-mediated immunosuppression in breast carcinomas. Cancer Discovery, 11(5), 1286–1305.PubMed
47.
go back to reference Plaschka, M., Benboubker, V., Grimont, M., Berthet, J., Tonon, L., Lopez, J., Le-Bouar, M., Balme, B., Tondeur, G., de la Fouchardière, A., Larue, L., Puisieux, A., Grinberg-Bleyer, Y., Bendriss-Vermare, N., Dubois, B., Caux, C., Dalle, S., & Caramel, J. (2022). ZEB1 transcription factor promotes immune escape in melanoma. Journal for Immunotherapy of Cancer, 10(3), e003484.PubMedPubMedCentral Plaschka, M., Benboubker, V., Grimont, M., Berthet, J., Tonon, L., Lopez, J., Le-Bouar, M., Balme, B., Tondeur, G., de la Fouchardière, A., Larue, L., Puisieux, A., Grinberg-Bleyer, Y., Bendriss-Vermare, N., Dubois, B., Caux, C., Dalle, S., & Caramel, J. (2022). ZEB1 transcription factor promotes immune escape in melanoma. Journal for Immunotherapy of Cancer, 10(3), e003484.PubMedPubMedCentral
48.
go back to reference Katsura, A., Tamura, Y., Hokari, S., Harada, M., Morikawa, M., Sakurai, T., Takahashi, K., Mizutani, A., Nishida, J., Yokoyama, Y., Morishita, Y., Murakami, T., Ehata, S., Miyazono, K., & Koinuma, D. (2017). ZEB1-regulated inflammatory phenotype in breast cancer cells. Molecular Oncology, 11(9), 1241–1262.PubMedPubMedCentral Katsura, A., Tamura, Y., Hokari, S., Harada, M., Morikawa, M., Sakurai, T., Takahashi, K., Mizutani, A., Nishida, J., Yokoyama, Y., Morishita, Y., Murakami, T., Ehata, S., Miyazono, K., & Koinuma, D. (2017). ZEB1-regulated inflammatory phenotype in breast cancer cells. Molecular Oncology, 11(9), 1241–1262.PubMedPubMedCentral
49.
go back to reference Taki, M., Abiko, K., Baba, T., Hamanishi, J., Yamaguchi, K., Murakami, R., Yamanoi, K., Horikawa, N., Hosoe, Y., Nakamura, E., Sugiyama, A., Mandai, M., Konishi, I., & Matsumura, N. (2018). SNAIL promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation. Nature Communications, 9(1), 1685.PubMedPubMedCentral Taki, M., Abiko, K., Baba, T., Hamanishi, J., Yamaguchi, K., Murakami, R., Yamanoi, K., Horikawa, N., Hosoe, Y., Nakamura, E., Sugiyama, A., Mandai, M., Konishi, I., & Matsumura, N. (2018). SNAIL promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation. Nature Communications, 9(1), 1685.PubMedPubMedCentral
50.
go back to reference Guo, Y., Lu, X., Chen, Y., Rendon, B., Mitchell, R. A., Cuatrecasas, M., Cortés, M., Postigo, A., Liu, Y., & Dean, D. C. (2021). Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells. Science. Advances, 7(21), eabd7455. Guo, Y., Lu, X., Chen, Y., Rendon, B., Mitchell, R. A., Cuatrecasas, M., Cortés, M., Postigo, A., Liu, Y., & Dean, D. C. (2021). Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells. Science. Advances, 7(21), eabd7455.
51.
go back to reference Qian, Y., Yao, W., Yang, T., Yang, Y., Liu, Y., Shen, Q., Zhang, J., Qi, W., & Wang, J. (2017). aPKC-ι/P-Sp1/SNAIL signaling induces epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma. Hepatology (Baltimore, Md.), 66(4), 1165–1182.PubMed Qian, Y., Yao, W., Yang, T., Yang, Y., Liu, Y., Shen, Q., Zhang, J., Qi, W., & Wang, J. (2017). aPKC-ι/P-Sp1/SNAIL signaling induces epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma. Hepatology (Baltimore, Md.), 66(4), 1165–1182.PubMed
52.
go back to reference Kuo, C. L., Chou, H. Y., Chiu, Y. C., Cheng, A. N., Fan, C. C., Chang, Y. N., Chen, C. H., Jiang, S. S., Chen, N. J., & Lee, A. Y. (2020). Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Letters, 474, 138–150.PubMed Kuo, C. L., Chou, H. Y., Chiu, Y. C., Cheng, A. N., Fan, C. C., Chang, Y. N., Chen, C. H., Jiang, S. S., Chen, N. J., & Lee, A. Y. (2020). Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Letters, 474, 138–150.PubMed
53.
go back to reference Ye, L. Y., Chen, W., Bai, X. L., Xu, X. Y., Zhang, Q., Xia, X. F., Sun, X., Li, G. G., Hu, Q. D., Fu, Q. H., & Liang, T. B. (2016). Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Research, 76(4), 818–830.PubMed Ye, L. Y., Chen, W., Bai, X. L., Xu, X. Y., Zhang, Q., Xia, X. F., Sun, X., Li, G. G., Hu, Q. D., Fu, Q. H., & Liang, T. B. (2016). Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Research, 76(4), 818–830.PubMed
54.
go back to reference Parajuli, G., Tekguc, M., Wing, J. B., Hashimoto, A., Okuzaki, D., Hirata, T., Sasaki, A., Itokazu, T., Handa, H., Sugino, H., Nishikawa, Y., Metwally, H., Kodama, Y., Tanaka, S., Sabe, H., Yamashita, T., Sakaguchi, S., Kishimoto, T., & Hashimoto, S. (2021). Arid5a promotes immune evasion by augmenting tryptophan metabolism and chemokine expression. Cancer Immunology Research, 9(8), 862–876.PubMed Parajuli, G., Tekguc, M., Wing, J. B., Hashimoto, A., Okuzaki, D., Hirata, T., Sasaki, A., Itokazu, T., Handa, H., Sugino, H., Nishikawa, Y., Metwally, H., Kodama, Y., Tanaka, S., Sabe, H., Yamashita, T., Sakaguchi, S., Kishimoto, T., & Hashimoto, S. (2021). Arid5a promotes immune evasion by augmenting tryptophan metabolism and chemokine expression. Cancer Immunology Research, 9(8), 862–876.PubMed
55.
go back to reference Wei, C., Yang, C., Wang, S., Shi, D., Zhang, C., Lin, X., Liu, Q., Dou, R., & Xiong, B. (2019). Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Molecular Cancer, 18(1), 64.PubMedPubMedCentral Wei, C., Yang, C., Wang, S., Shi, D., Zhang, C., Lin, X., Liu, Q., Dou, R., & Xiong, B. (2019). Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Molecular Cancer, 18(1), 64.PubMedPubMedCentral
56.
go back to reference Goyette, M. A., Elkholi, I. E., Apcher, C., Kuasne, H., Rothlin, C. V., Muller, W. J., Richard, D. E., Park, M., Gratton, J. P., & Côté, J. F. (2021). Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels. Proceedings of the National Academy of Sciences of the United States of America, 118(29), e2023868118.PubMedPubMedCentral Goyette, M. A., Elkholi, I. E., Apcher, C., Kuasne, H., Rothlin, C. V., Muller, W. J., Richard, D. E., Park, M., Gratton, J. P., & Côté, J. F. (2021). Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels. Proceedings of the National Academy of Sciences of the United States of America, 118(29), e2023868118.PubMedPubMedCentral
57.
go back to reference Yang, C., Dou, R., Wei, C., Liu, K., Shi, D., Zhang, C., Liu, Q., Wang, S., & Xiong, B. (2021). Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Molecular Therapy, 29(6), 2088–2107.PubMedPubMedCentral Yang, C., Dou, R., Wei, C., Liu, K., Shi, D., Zhang, C., Liu, Q., Wang, S., & Xiong, B. (2021). Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Molecular Therapy, 29(6), 2088–2107.PubMedPubMedCentral
58.
go back to reference Hanahan, D., & Coussens, L. M. (2012). Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell, 21(3), 309–322.PubMed Hanahan, D., & Coussens, L. M. (2012). Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell, 21(3), 309–322.PubMed
59.
go back to reference Hui, L., & Chen, Y. (2015). Tumor microenvironment: Sanctuary of the devil. Cancer Letters, 368(1), 7–13.PubMed Hui, L., & Chen, Y. (2015). Tumor microenvironment: Sanctuary of the devil. Cancer Letters, 368(1), 7–13.PubMed
60.
go back to reference Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., & Ohta, T. (2016). Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. Gastric Cancer, 19(4), 1052–1065.PubMed Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., & Ohta, T. (2016). Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. Gastric Cancer, 19(4), 1052–1065.PubMed
61.
go back to reference Yin, S., Huang, J., Li, Z., Zhang, J., Luo, J., Lu, C., Xu, H., & Xu, H. (2017). The prognostic and clinicopathological significance of tumor-associated macrophages in patients with gastric cancer: A meta-analysis. PloS One, 12(1), e0170042.PubMedPubMedCentral Yin, S., Huang, J., Li, Z., Zhang, J., Luo, J., Lu, C., Xu, H., & Xu, H. (2017). The prognostic and clinicopathological significance of tumor-associated macrophages in patients with gastric cancer: A meta-analysis. PloS One, 12(1), e0170042.PubMedPubMedCentral
62.
go back to reference Yang, M., Li, Z., Ren, M., Li, S., Zhang, L., Zhang, X., & Liu, F. (2018). Stromal infiltration of tumor-associated macrophages conferring poor prognosis of patients with basal-like breast carcinoma. Journal of Cancer, 9(13), 2308–2316.PubMedPubMedCentral Yang, M., Li, Z., Ren, M., Li, S., Zhang, L., Zhang, X., & Liu, F. (2018). Stromal infiltration of tumor-associated macrophages conferring poor prognosis of patients with basal-like breast carcinoma. Journal of Cancer, 9(13), 2308–2316.PubMedPubMedCentral
63.
go back to reference Zhang, Q., He, Y., Luo, N., Patel, S. J., Han, Y., Gao, R., Modak, M., Carotta, S., Haslinger, C., Kind, D., Peet, G. W., Zhong, G., Lu, S., Zhu, W., Mao, Y., Xiao, M., Bergmann, M., Hu, X., Kerkar, S. P., et al. (2019). Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell, 179(4), 829–845.e20.PubMed Zhang, Q., He, Y., Luo, N., Patel, S. J., Han, Y., Gao, R., Modak, M., Carotta, S., Haslinger, C., Kind, D., Peet, G. W., Zhong, G., Lu, S., Zhu, W., Mao, Y., Xiao, M., Bergmann, M., Hu, X., Kerkar, S. P., et al. (2019). Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell, 179(4), 829–845.e20.PubMed
64.
go back to reference Shrivastava, R., & Shukla, N. (2019). Attributes of alternatively activated (M2) macrophages. Life Sciences, 224, 222–231.PubMed Shrivastava, R., & Shukla, N. (2019). Attributes of alternatively activated (M2) macrophages. Life Sciences, 224, 222–231.PubMed
65.
go back to reference Mir, F. A., Contreras-Ruiz, L., & Masli, S. (2015). Thrombospondin-1-dependent immune regulation by transforming growth factor-β2-exposed antigen-presenting cells. Immunology, 146(4), 547–556.PubMedPubMedCentral Mir, F. A., Contreras-Ruiz, L., & Masli, S. (2015). Thrombospondin-1-dependent immune regulation by transforming growth factor-β2-exposed antigen-presenting cells. Immunology, 146(4), 547–556.PubMedPubMedCentral
66.
go back to reference Dave, M. (2017). TSP-1-mediated induction of T regulatory cell by adipose-derived mesenchymal stem cells: a mechanism of immunosuppression. Digestive Diseases and Sciences, 62(8), 1975–1976.PubMedPubMedCentral Dave, M. (2017). TSP-1-mediated induction of T regulatory cell by adipose-derived mesenchymal stem cells: a mechanism of immunosuppression. Digestive Diseases and Sciences, 62(8), 1975–1976.PubMedPubMedCentral
67.
go back to reference Nath, P. R., Pal-Nath, D., Mandal, A., Cam, M. C., Schwartz, A. L., & Roberts, D. D. (2019). Natural killer cell recruitment and activation are regulated by CD47 expression in the tumor microenvironment. Cancer Immunology Research, 7(9), 1547–1561.PubMedPubMedCentral Nath, P. R., Pal-Nath, D., Mandal, A., Cam, M. C., Schwartz, A. L., & Roberts, D. D. (2019). Natural killer cell recruitment and activation are regulated by CD47 expression in the tumor microenvironment. Cancer Immunology Research, 7(9), 1547–1561.PubMedPubMedCentral
68.
go back to reference Hosseini, H., Obradović, M. M. S., Hoffmann, M., Harper, K. L., Sosa, M. S., Werner-Klein, M., Nanduri, L. K., Werno, C., Ehrl, C., Maneck, M., Patwary, N., Haunschild, G., Gužvić, M., Reimelt, C., Grauvogl, M., Eichner, N., Weber, F., Hartkopf, A. D., Taran, F. A., et al. (2016). Early dissemination seeds metastasis in breast cancer. Nature, 540(7634), 552–558.PubMedPubMedCentral Hosseini, H., Obradović, M. M. S., Hoffmann, M., Harper, K. L., Sosa, M. S., Werner-Klein, M., Nanduri, L. K., Werno, C., Ehrl, C., Maneck, M., Patwary, N., Haunschild, G., Gužvić, M., Reimelt, C., Grauvogl, M., Eichner, N., Weber, F., Hartkopf, A. D., Taran, F. A., et al. (2016). Early dissemination seeds metastasis in breast cancer. Nature, 540(7634), 552–558.PubMedPubMedCentral
69.
go back to reference Dongre, A., Rashidian, M., Reinhardt, F., Bagnato, A., Keckesova, Z., Ploegh, H. L., & Weinberg, R. A. (2017). Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Research, 77(15), 3982–3989.PubMedPubMedCentral Dongre, A., Rashidian, M., Reinhardt, F., Bagnato, A., Keckesova, Z., Ploegh, H. L., & Weinberg, R. A. (2017). Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Research, 77(15), 3982–3989.PubMedPubMedCentral
70.
go back to reference Terry, S., Savagner, P., Ortiz-Cuaran, S., Mahjoubi, L., Saintigny, P., Thiery, J. P., & Chouaib, S. (2017). New insights into the role of EMT in tumor immune escape. Molecular Oncology, 11(7), 824–846.PubMedPubMedCentral Terry, S., Savagner, P., Ortiz-Cuaran, S., Mahjoubi, L., Saintigny, P., Thiery, J. P., & Chouaib, S. (2017). New insights into the role of EMT in tumor immune escape. Molecular Oncology, 11(7), 824–846.PubMedPubMedCentral
71.
go back to reference Rückerl, D., & Allen, J. E. (2014). Macrophage proliferation, provenance, and plasticity in macroparasite infection. Immunological Reviews, 262(1), 113–133.PubMedPubMedCentral Rückerl, D., & Allen, J. E. (2014). Macrophage proliferation, provenance, and plasticity in macroparasite infection. Immunological Reviews, 262(1), 113–133.PubMedPubMedCentral
72.
go back to reference Zhu, J., Zhi, Q., Zhou, B. P., Tao, M., Liu, J., & Li, W. (2016). The role of tumor associated macrophages in the tumor microenvironment: Mechanism and functions. Anti-Cancer Agents In Medicinal Chemistry, 16(9), 1133–1141.PubMed Zhu, J., Zhi, Q., Zhou, B. P., Tao, M., Liu, J., & Li, W. (2016). The role of tumor associated macrophages in the tumor microenvironment: Mechanism and functions. Anti-Cancer Agents In Medicinal Chemistry, 16(9), 1133–1141.PubMed
73.
go back to reference Helm, O., Held-Feindt, J., Grage-Griebenow, E., Reiling, N., Ungefroren, H., Vogel, I., Krüger, U., Becker, T., Ebsen, M., Röcken, C., Kabelitz, D., Schäfer, H., & Sebens, S. (2014). Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis. International Journal of Cancer, 135(4), 843–861.PubMed Helm, O., Held-Feindt, J., Grage-Griebenow, E., Reiling, N., Ungefroren, H., Vogel, I., Krüger, U., Becker, T., Ebsen, M., Röcken, C., Kabelitz, D., Schäfer, H., & Sebens, S. (2014). Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis. International Journal of Cancer, 135(4), 843–861.PubMed
74.
go back to reference Mishra, A. K., Banday, S., Bharadwaj, R., Ali, A., Rashid, R., Kulshreshtha, A., & Malonia, S. K. (2022). Macrophages as a potential immunotherapeutic target in solid cancers. Vaccines, 11(1), 55.PubMedPubMedCentral Mishra, A. K., Banday, S., Bharadwaj, R., Ali, A., Rashid, R., Kulshreshtha, A., & Malonia, S. K. (2022). Macrophages as a potential immunotherapeutic target in solid cancers. Vaccines, 11(1), 55.PubMedPubMedCentral
76.
go back to reference Pinto, M. L., Rios, E., Durães, C., Ribeiro, R., Machado, J. C., Mantovani, A., Barbosa, M. A., Carneiro, F., & Oliveira, M. J. (2019). The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Frontiers in Immunology, 10, 1875.PubMedPubMedCentral Pinto, M. L., Rios, E., Durães, C., Ribeiro, R., Machado, J. C., Mantovani, A., Barbosa, M. A., Carneiro, F., & Oliveira, M. J. (2019). The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Frontiers in Immunology, 10, 1875.PubMedPubMedCentral
77.
go back to reference Bonde, A. K., Tischler, V., Kumar, S., Soltermann, A., & Schwendener, R. A. (2012). Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors. BMC Cancer, 12, 35.PubMedPubMedCentral Bonde, A. K., Tischler, V., Kumar, S., Soltermann, A., & Schwendener, R. A. (2012). Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors. BMC Cancer, 12, 35.PubMedPubMedCentral
78.
go back to reference Shahbaz, S., Bozorgmehr, N., Koleva, P., Namdar, A., Jovel, J., Fava, R. A., & Elahi, S. (2018). CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β. PLoS Biology, 16(12), e2006649.PubMedPubMedCentral Shahbaz, S., Bozorgmehr, N., Koleva, P., Namdar, A., Jovel, J., Fava, R. A., & Elahi, S. (2018). CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β. PLoS Biology, 16(12), e2006649.PubMedPubMedCentral
79.
go back to reference Hao, Y., Baker, D., & Ten Dijke, P. (2019). TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. International Journal of Molecular Sciences, 20(11), 2767.PubMedPubMedCentral Hao, Y., Baker, D., & Ten Dijke, P. (2019). TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. International Journal of Molecular Sciences, 20(11), 2767.PubMedPubMedCentral
80.
go back to reference Liu, M., Li, S., & Li, M. O. (2018). TGF-β control of adaptive immune tolerance: A break from Treg cells. Bioessays : News and Reviews In Molecular, Cellular And Developmental Biology, 40(11), e1800063.PubMed Liu, M., Li, S., & Li, M. O. (2018). TGF-β control of adaptive immune tolerance: A break from Treg cells. Bioessays : News and Reviews In Molecular, Cellular And Developmental Biology, 40(11), e1800063.PubMed
81.
go back to reference Crane, C. A., Han, S. J., Barry, J. J., Ahn, B. J., Lanier, L. L., & Parsa, A. T. (2010). TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro-oncology, 12(1), 7–13.PubMed Crane, C. A., Han, S. J., Barry, J. J., Ahn, B. J., Lanier, L. L., & Parsa, A. T. (2010). TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro-oncology, 12(1), 7–13.PubMed
82.
go back to reference Viel, S., Marçais, A., Guimaraes, F. S., Loftus, R., Rabilloud, J., Grau, M., Degouve, S., Djebali, S., Sanlaville, A., Charrier, E., Bienvenu, J., Marie, J. C., Caux, C., Marvel, J., Town, L., Huntington, N. D., Bartholin, L., Finlay, D., Smyth, M. J., & Walzer, T. (2016). TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway. Science Signaling, 9(415), ra19.PubMed Viel, S., Marçais, A., Guimaraes, F. S., Loftus, R., Rabilloud, J., Grau, M., Degouve, S., Djebali, S., Sanlaville, A., Charrier, E., Bienvenu, J., Marie, J. C., Caux, C., Marvel, J., Town, L., Huntington, N. D., Bartholin, L., Finlay, D., Smyth, M. J., & Walzer, T. (2016). TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway. Science Signaling, 9(415), ra19.PubMed
83.
go back to reference Gregory, P. A., Bracken, C. P., Smith, E., Bert, A. G., Wright, J. A., Roslan, S., Morris, M., Wyatt, L., Farshid, G., Lim, Y. Y., Lindeman, G. J., Shannon, M. F., Drew, P. A., Khew-Goodall, Y., & Goodall, G. J. (2011). An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Molecular Biology of the Cell, 22(10), 1686–1698.PubMedPubMedCentral Gregory, P. A., Bracken, C. P., Smith, E., Bert, A. G., Wright, J. A., Roslan, S., Morris, M., Wyatt, L., Farshid, G., Lim, Y. Y., Lindeman, G. J., Shannon, M. F., Drew, P. A., Khew-Goodall, Y., & Goodall, G. J. (2011). An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Molecular Biology of the Cell, 22(10), 1686–1698.PubMedPubMedCentral
84.
go back to reference David, J. M., Dominguez, C., McCampbell, K. K., Gulley, J. L., Schlom, J., & Palena, C. (2017). A novel bifunctional anti-PD-L1/TGF-β Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells. Oncoimmunology, 6(10), e1349589.PubMedPubMedCentral David, J. M., Dominguez, C., McCampbell, K. K., Gulley, J. L., Schlom, J., & Palena, C. (2017). A novel bifunctional anti-PD-L1/TGF-β Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells. Oncoimmunology, 6(10), e1349589.PubMedPubMedCentral
85.
go back to reference Zhu, P., Baek, S. H., Bourk, E. M., Ohgi, K. A., Garcia-Bassets, I., Sanjo, H., Akira, S., Kotol, P. F., Glass, C. K., Rosenfeld, M. G., & Rose, D. W. (2006). Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell, 124(3), 615–629.PubMed Zhu, P., Baek, S. H., Bourk, E. M., Ohgi, K. A., Garcia-Bassets, I., Sanjo, H., Akira, S., Kotol, P. F., Glass, C. K., Rosenfeld, M. G., & Rose, D. W. (2006). Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell, 124(3), 615–629.PubMed
86.
go back to reference Izumi, K., Fang, L. Y., Mizokami, A., Namiki, M., Li, L., Lin, W. J., & Chang, C. (2013). Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Molecular Medicine, 5(9), 1383–1401.PubMedPubMedCentral Izumi, K., Fang, L. Y., Mizokami, A., Namiki, M., Li, L., Lin, W. J., & Chang, C. (2013). Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Molecular Medicine, 5(9), 1383–1401.PubMedPubMedCentral
87.
go back to reference Antony, J., & Huang, R. Y. (2017). AXL-Driven EMT state as a targetable conduit in cancer. Cancer Research, 77(14), 3725–3732.PubMed Antony, J., & Huang, R. Y. (2017). AXL-Driven EMT state as a targetable conduit in cancer. Cancer Research, 77(14), 3725–3732.PubMed
88.
go back to reference Santamaria, P. G., Moreno-Bueno, G., Portillo, F., & Cano, A. (2017). EMT: Present and future in clinical oncology. Molecular Oncology, 11(7), 718–738.PubMedPubMedCentral Santamaria, P. G., Moreno-Bueno, G., Portillo, F., & Cano, A. (2017). EMT: Present and future in clinical oncology. Molecular Oncology, 11(7), 718–738.PubMedPubMedCentral
89.
go back to reference Terry, S., Abdou, A., Engelsen, A. S. T., Buart, S., Dessen, P., Corgnac, S., Collares, D., Meurice, G., Gausdal, G., Baud, V., Saintigny, P., Lorens, J. B., Thiery, J. P., Mami-Chouaib, F., & Chouaib, S. (2019). AXL targeting overcomes human lung cancer cell resistance to NK- and CTL-mediated cytotoxicity. Cancer Immunology Research, 7(11), 1789–1802.PubMed Terry, S., Abdou, A., Engelsen, A. S. T., Buart, S., Dessen, P., Corgnac, S., Collares, D., Meurice, G., Gausdal, G., Baud, V., Saintigny, P., Lorens, J. B., Thiery, J. P., Mami-Chouaib, F., & Chouaib, S. (2019). AXL targeting overcomes human lung cancer cell resistance to NK- and CTL-mediated cytotoxicity. Cancer Immunology Research, 7(11), 1789–1802.PubMed
90.
go back to reference Xiong, X., Liao, X., Qiu, S., Xu, H., Zhang, S., Wang, S., Ai, J., & Yang, L. (2022). CXCL8 in tumor biology and its implications for clinical translation. Frontiers in Molecular Biosciences, 9, 723846.PubMedPubMedCentral Xiong, X., Liao, X., Qiu, S., Xu, H., Zhang, S., Wang, S., Ai, J., & Yang, L. (2022). CXCL8 in tumor biology and its implications for clinical translation. Frontiers in Molecular Biosciences, 9, 723846.PubMedPubMedCentral
91.
go back to reference Cheng, Y., Ma, X. L., Wei, Y. Q., & Wei, X. W. (2019). Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases. Biochimica et Biophysica Acta. Reviews on. Cancer, 1871(2), 289–312. Cheng, Y., Ma, X. L., Wei, Y. Q., & Wei, X. W. (2019). Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases. Biochimica et Biophysica Acta. Reviews on. Cancer, 1871(2), 289–312.
92.
go back to reference Serafini, P., Mgebroff, S., Noonan, K., & Borrello, I. (2008). Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Research, 68(13), 5439–5449.PubMedPubMedCentral Serafini, P., Mgebroff, S., Noonan, K., & Borrello, I. (2008). Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Research, 68(13), 5439–5449.PubMedPubMedCentral
93.
go back to reference Hanson, E. M., Clements, V. K., Sinha, P., Ilkovitch, D., & Ostrand-Rosenberg, S. (2009). Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. Journal of Immunology (Baltimore, Md.: 1950), 183(2), 937–944.PubMed Hanson, E. M., Clements, V. K., Sinha, P., Ilkovitch, D., & Ostrand-Rosenberg, S. (2009). Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. Journal of Immunology (Baltimore, Md.: 1950), 183(2), 937–944.PubMed
94.
go back to reference Geis-Asteggiante, L., Belew, A. T., Clements, V. K., Edwards, N. J., Ostrand-Rosenberg, S., El-Sayed, N. M., & Fenselau, C. (2018). Differential content of proteins, mRNAs, and miRNAs suggests that MDSC and their exosomes may mediate distinct immune suppressive functions. Journal of Proteome Research, 17(1), 486–498.PubMed Geis-Asteggiante, L., Belew, A. T., Clements, V. K., Edwards, N. J., Ostrand-Rosenberg, S., El-Sayed, N. M., & Fenselau, C. (2018). Differential content of proteins, mRNAs, and miRNAs suggests that MDSC and their exosomes may mediate distinct immune suppressive functions. Journal of Proteome Research, 17(1), 486–498.PubMed
95.
go back to reference Mao, F. Y., Zhao, Y. L., Lv, Y. P., Teng, Y. S., Kong, H., Liu, Y. G., Wu, X. L., Hao, C. J., Chen, W., Duan, M. B., Han, B., Ma, Q., Wang, T. T., Peng, L. S., Zhang, J. Y., Cheng, P., Su, C. Y., Fu, X. L., Zou, Q. M., et al. (2018). CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer. Cell Death & Disease, 9(7), 763. Mao, F. Y., Zhao, Y. L., Lv, Y. P., Teng, Y. S., Kong, H., Liu, Y. G., Wu, X. L., Hao, C. J., Chen, W., Duan, M. B., Han, B., Ma, Q., Wang, T. T., Peng, L. S., Zhang, J. Y., Cheng, P., Su, C. Y., Fu, X. L., Zou, Q. M., et al. (2018). CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer. Cell Death & Disease, 9(7), 763.
96.
go back to reference Chi, N., Tan, Z., Ma, K., Bao, L., & Yun, Z. (2014). Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer. International Journal of Clinical and Experimental Medicine, 7(10), 3181–3192.PubMedPubMedCentral Chi, N., Tan, Z., Ma, K., Bao, L., & Yun, Z. (2014). Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer. International Journal of Clinical and Experimental Medicine, 7(10), 3181–3192.PubMedPubMedCentral
97.
go back to reference Jiang, Y., & Zhan, H. (2020). Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion. Cancer Letters, 468, 72–81.PubMed Jiang, Y., & Zhan, H. (2020). Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion. Cancer Letters, 468, 72–81.PubMed
98.
go back to reference Noman, M. Z., Janji, B., Abdou, A., Hasmim, M., Terry, S., Tan, T. Z., Mami-Chouaib, F., Thiery, J. P., & Chouaib, S. (2017). The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200. Oncoimmunology, 6(1), e1263412.PubMedPubMedCentral Noman, M. Z., Janji, B., Abdou, A., Hasmim, M., Terry, S., Tan, T. Z., Mami-Chouaib, F., Thiery, J. P., & Chouaib, S. (2017). The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200. Oncoimmunology, 6(1), e1263412.PubMedPubMedCentral
99.
go back to reference Mathew, M., Safyan, R. A., & Shu, C. A. (2017). PD-L1 as a biomarker in NSCLC: Challenges and future directions. Annals of Translational Medicine, 5(18), 375.PubMedPubMedCentral Mathew, M., Safyan, R. A., & Shu, C. A. (2017). PD-L1 as a biomarker in NSCLC: Challenges and future directions. Annals of Translational Medicine, 5(18), 375.PubMedPubMedCentral
100.
go back to reference Kim, S., Koh, J., Kim, M. Y., Kwon, D., Go, H., Kim, Y. A., Jeon, Y. K., & Chung, D. H. (2016). PD-L1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung. Human Pathology, 58, 7–14.PubMed Kim, S., Koh, J., Kim, M. Y., Kwon, D., Go, H., Kim, Y. A., Jeon, Y. K., & Chung, D. H. (2016). PD-L1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung. Human Pathology, 58, 7–14.PubMed
101.
go back to reference Ock, C. Y., Kim, S., Keam, B., Kim, M., Kim, T. M., Kim, J. H., Jeon, Y. K., Lee, J. S., Kwon, S. K., Hah, J. H., Kwon, T. K., Kim, D. W., Wu, H. G., Sung, M. W., & Heo, D. S. (2016). PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget, 7(13), 15901–15914.PubMedPubMedCentral Ock, C. Y., Kim, S., Keam, B., Kim, M., Kim, T. M., Kim, J. H., Jeon, Y. K., Lee, J. S., Kwon, S. K., Hah, J. H., Kwon, T. K., Kim, D. W., Wu, H. G., Sung, M. W., & Heo, D. S. (2016). PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget, 7(13), 15901–15914.PubMedPubMedCentral
102.
go back to reference Tsutsumi, S., Saeki, H., Nakashima, Y., Ito, S., Oki, E., Morita, M., Oda, Y., Okano, S., & Maehara, Y. (2017). Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Science, 108(6), 1119–1127.PubMedPubMedCentral Tsutsumi, S., Saeki, H., Nakashima, Y., Ito, S., Oki, E., Morita, M., Oda, Y., Okano, S., & Maehara, Y. (2017). Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Science, 108(6), 1119–1127.PubMedPubMedCentral
103.
go back to reference Qiu, X. Y., Hu, D. X., Chen, W. Q., Chen, R. Q., Qian, S. R., Li, C. Y., Li, Y. J., Xiong, X. X., Liu, D., Pan, F., Yu, S. B., & Chen, X. Q. (2018). PD-L1 confers glioblastoma multiforme malignancy via Ras binding and Ras/Erk/EMT activation. Biochimica et biophysica acta. Molecular Basis of Disease, 1864(5 Pt A), 1754–1769.PubMed Qiu, X. Y., Hu, D. X., Chen, W. Q., Chen, R. Q., Qian, S. R., Li, C. Y., Li, Y. J., Xiong, X. X., Liu, D., Pan, F., Yu, S. B., & Chen, X. Q. (2018). PD-L1 confers glioblastoma multiforme malignancy via Ras binding and Ras/Erk/EMT activation. Biochimica et biophysica acta. Molecular Basis of Disease, 1864(5 Pt A), 1754–1769.PubMed
104.
go back to reference Alsuliman, A., Colak, D., Al-Harazi, O., Fitwi, H., Tulbah, A., Al-Tweigeri, T., Al-Alwan, M., & Ghebeh, H. (2015). Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: Significance in claudin-low breast cancer cells. Molecular Cancer, 14, 149.PubMedPubMedCentral Alsuliman, A., Colak, D., Al-Harazi, O., Fitwi, H., Tulbah, A., Al-Tweigeri, T., Al-Alwan, M., & Ghebeh, H. (2015). Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: Significance in claudin-low breast cancer cells. Molecular Cancer, 14, 149.PubMedPubMedCentral
105.
go back to reference Bouillez, A., Rajabi, H., Jin, C., Samur, M., Tagde, A., Alam, M., Hiraki, M., Maeda, T., Hu, X., Adeegbe, D., Kharbanda, S., Wong, K. K., & Kufe, D. (2017). MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer. Oncogene, 36(28), 4037–4046.PubMedPubMedCentral Bouillez, A., Rajabi, H., Jin, C., Samur, M., Tagde, A., Alam, M., Hiraki, M., Maeda, T., Hu, X., Adeegbe, D., Kharbanda, S., Wong, K. K., & Kufe, D. (2017). MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer. Oncogene, 36(28), 4037–4046.PubMedPubMedCentral
106.
go back to reference Maeda, T., Hiraki, M., Jin, C., Rajabi, H., Tagde, A., Alam, M., Bouillez, A., Hu, X., Suzuki, Y., Miyo, M., Hata, T., Hinohara, K., & Kufe, D. (2018). MUC1-C induces PD-L1 and immune evasion in triple-negative breast cancer. Cancer research, 78(1), 205–215.PubMed Maeda, T., Hiraki, M., Jin, C., Rajabi, H., Tagde, A., Alam, M., Bouillez, A., Hu, X., Suzuki, Y., Miyo, M., Hata, T., Hinohara, K., & Kufe, D. (2018). MUC1-C induces PD-L1 and immune evasion in triple-negative breast cancer. Cancer research, 78(1), 205–215.PubMed
107.
go back to reference Kumar, S., Davra, V., Obr, A. E., Geng, K., Wood, T. L., De Lorenzo, M. S., & Birge, R. B. (2017). Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer. Oncoimmunology, 7(1), e1376155.PubMedPubMedCentral Kumar, S., Davra, V., Obr, A. E., Geng, K., Wood, T. L., De Lorenzo, M. S., & Birge, R. B. (2017). Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer. Oncoimmunology, 7(1), e1376155.PubMedPubMedCentral
108.
go back to reference Suda, K., Rozeboom, L., Rivard, C. J., Yu, H., Ellison, K., Melnick, M. A. C., Hinz, T. K., Chan, D., Heasley, L. E., Politi, K., Mitsudomi, T., & Hirsch, F. R. (2017). Therapy-induced E-cadherin downregulation alters expression of programmed death ligand-1 in lung cancer cells. Lung Cancer (Amsterdam, Netherlands), 109, 1–8.PubMed Suda, K., Rozeboom, L., Rivard, C. J., Yu, H., Ellison, K., Melnick, M. A. C., Hinz, T. K., Chan, D., Heasley, L. E., Politi, K., Mitsudomi, T., & Hirsch, F. R. (2017). Therapy-induced E-cadherin downregulation alters expression of programmed death ligand-1 in lung cancer cells. Lung Cancer (Amsterdam, Netherlands), 109, 1–8.PubMed
109.
go back to reference Martinez-Ciarpaglini, C., Oltra, S., Roselló, S., Roda, D., Mongort, C., Carrasco, F., Gonzalez, J., Santonja, F., Tarazona, N., Huerta, M., Espí, A., Ribas, G., Ferrández, A., Navarro, S., & Cervantes, A. (2019). Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression. Modern Pathology, Inc, 32(2), 306–313. Martinez-Ciarpaglini, C., Oltra, S., Roselló, S., Roda, D., Mongort, C., Carrasco, F., Gonzalez, J., Santonja, F., Tarazona, N., Huerta, M., Espí, A., Ribas, G., Ferrández, A., Navarro, S., & Cervantes, A. (2019). Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression. Modern Pathology, Inc, 32(2), 306–313.
110.
go back to reference Ding, X., Ji, J., Jiang, J., Cai, Q., Wang, C., Shi, M., Yu, Y., Zhu, Z., & Zhang, J. (2018). HGF-mediated crosstalk between cancer-associated fibroblasts and MET-unamplified gastric cancer cells activates coordinated tumorigenesis and metastasis. Cell Death & Disease, 9(9), 867. Ding, X., Ji, J., Jiang, J., Cai, Q., Wang, C., Shi, M., Yu, Y., Zhu, Z., & Zhang, J. (2018). HGF-mediated crosstalk between cancer-associated fibroblasts and MET-unamplified gastric cancer cells activates coordinated tumorigenesis and metastasis. Cell Death & Disease, 9(9), 867.
111.
go back to reference Dong, Y., Zheng, Q., Wang, Z., Lin, X., You, Y., Wu, S., Wang, Y., Hu, C., Xie, X., Chen, J., Gao, D., Zhao, Y., Wu, W., Liu, Y., Ren, Z., Chen, R., & Cui, J. (2019). Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis. Journal of Hematology & Oncology, 12(1), 112. Dong, Y., Zheng, Q., Wang, Z., Lin, X., You, Y., Wu, S., Wang, Y., Hu, C., Xie, X., Chen, J., Gao, D., Zhao, Y., Wu, W., Liu, Y., Ren, Z., Chen, R., & Cui, J. (2019). Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis. Journal of Hematology & Oncology, 12(1), 112.
112.
go back to reference Zhang, K., Corsa, C. A., Ponik, S. M., Prior, J. L., Piwnica-Worms, D., Eliceiri, K. W., Keely, P. J., & Longmore, G. D. (2013). The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature Cell Biology, 15(6), 677–687.PubMedPubMedCentral Zhang, K., Corsa, C. A., Ponik, S. M., Prior, J. L., Piwnica-Worms, D., Eliceiri, K. W., Keely, P. J., & Longmore, G. D. (2013). The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature Cell Biology, 15(6), 677–687.PubMedPubMedCentral
113.
go back to reference Sim, W. J., Iyengar, P. V., Lama, D., Lui, S. K. L., Ng, H. C., Haviv-Shapira, L., Domany, E., Kappei, D., Tan, T. Z., Saei, A., Jaynes, P. W., Verma, C. S., Kumar, A. P., Rouanne, M., Ha, H. K., Radulescu, C., Ten Dijke, P., Eichhorn, P. J. A., & Thiery, J. P. (2019). c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression. Nature Communications, 10(1), 4349.PubMedPubMedCentral Sim, W. J., Iyengar, P. V., Lama, D., Lui, S. K. L., Ng, H. C., Haviv-Shapira, L., Domany, E., Kappei, D., Tan, T. Z., Saei, A., Jaynes, P. W., Verma, C. S., Kumar, A. P., Rouanne, M., Ha, H. K., Radulescu, C., Ten Dijke, P., Eichhorn, P. J. A., & Thiery, J. P. (2019). c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression. Nature Communications, 10(1), 4349.PubMedPubMedCentral
114.
go back to reference Glodde, N., Bald, T., van den Boorn-Konijnenberg, D., Nakamura, K., O'Donnell, J. S., Szczepanski, S., Brandes, M., Eickhoff, S., Das, I., Shridhar, N., Hinze, D., Rogava, M., van der Sluis, T. C., Ruotsalainen, J. J., Gaffal, E., Landsberg, J., Ludwig, K. U., Wilhelm, C., Riek-Burchardt, M., et al. (2017). Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy. Immunity, 47(4), 789–802.e9.PubMed Glodde, N., Bald, T., van den Boorn-Konijnenberg, D., Nakamura, K., O'Donnell, J. S., Szczepanski, S., Brandes, M., Eickhoff, S., Das, I., Shridhar, N., Hinze, D., Rogava, M., van der Sluis, T. C., Ruotsalainen, J. J., Gaffal, E., Landsberg, J., Ludwig, K. U., Wilhelm, C., Riek-Burchardt, M., et al. (2017). Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy. Immunity, 47(4), 789–802.e9.PubMed
115.
go back to reference Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019). Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Molecular Cancer, 18(1), 157.PubMedPubMedCentral Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019). Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Molecular Cancer, 18(1), 157.PubMedPubMedCentral
116.
go back to reference Hou, P. C., Li, Y. H., Lin, S. C., Lin, S. C., Lee, J. C., Lin, B. W., Liou, J. P., Chang, J. Y., Kuo, C. C., Liu, Y. M., Sun, H. S., & Tsai, S. J. (2017). Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness. Cancer Research, 77(16), 4305–4316.PubMed Hou, P. C., Li, Y. H., Lin, S. C., Lin, S. C., Lee, J. C., Lin, B. W., Liou, J. P., Chang, J. Y., Kuo, C. C., Liu, Y. M., Sun, H. S., & Tsai, S. J. (2017). Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness. Cancer Research, 77(16), 4305–4316.PubMed
117.
go back to reference Calin, G. A., & Pardini, B. (2019). Mir-roring hypoxia in EGFR-TKI tolerance. Nature Metabolism, 1(4), 418–419.PubMed Calin, G. A., & Pardini, B. (2019). Mir-roring hypoxia in EGFR-TKI tolerance. Nature Metabolism, 1(4), 418–419.PubMed
118.
go back to reference Ye, Y., Hu, Q., Chen, H., Liang, K., Yuan, Y., Xiang, Y., Ruan, H., Zhang, Z., Song, A., Zhang, H., Liu, L., Diao, L., Lou, Y., Zhou, B., Wang, L., Zhou, S., Gao, J., Jonasch, E., Lin, S. H., et al. (2019). Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nature Metabolism, 1(4), 431–444.PubMedPubMedCentral Ye, Y., Hu, Q., Chen, H., Liang, K., Yuan, Y., Xiang, Y., Ruan, H., Zhang, Z., Song, A., Zhang, H., Liu, L., Diao, L., Lou, Y., Zhou, B., Wang, L., Zhou, S., Gao, J., Jonasch, E., Lin, S. H., et al. (2019). Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nature Metabolism, 1(4), 431–444.PubMedPubMedCentral
119.
go back to reference Gonzalez, D. M., & Medici, D. (2014). Signaling mechanisms of the epithelial-mesenchymal transition. Science Signaling, 7(344), re8.PubMedPubMedCentral Gonzalez, D. M., & Medici, D. (2014). Signaling mechanisms of the epithelial-mesenchymal transition. Science Signaling, 7(344), re8.PubMedPubMedCentral
120.
go back to reference Sahlgren, C., Gustafsson, M. V., Jin, S., Poellinger, L., & Lendahl, U. (2008). Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proceedings of the National Academy of Sciences of the United States of America, 105(17), 6392–6397.PubMedPubMedCentral Sahlgren, C., Gustafsson, M. V., Jin, S., Poellinger, L., & Lendahl, U. (2008). Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proceedings of the National Academy of Sciences of the United States of America, 105(17), 6392–6397.PubMedPubMedCentral
121.
go back to reference Schito, L., & Semenza, G. L. (2016). Hypoxia-inducible factors: Master regulators of cancer progression. Trends in Cancer, 2(12), 758–770.PubMed Schito, L., & Semenza, G. L. (2016). Hypoxia-inducible factors: Master regulators of cancer progression. Trends in Cancer, 2(12), 758–770.PubMed
122.
go back to reference Wang, J., Tian, L., Khan, M. N., Zhang, L., Chen, Q., Zhao, Y., Yan, Q., Fu, L., & Liu, J. (2018). Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness. Cancer Letters, 415, 73–85.PubMed Wang, J., Tian, L., Khan, M. N., Zhang, L., Chen, Q., Zhao, Y., Yan, Q., Fu, L., & Liu, J. (2018). Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness. Cancer Letters, 415, 73–85.PubMed
123.
go back to reference Qin, Y., Liu, H. J., Li, M., Zhai, D. H., Tang, Y. H., Yang, L., Qiao, K. L., Yang, J. H., Zhong, W. L., Zhang, Q., Liu, Y. R., Yang, G., Sun, T., & Yang, C. (2018). Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway. EBioMedicine, 38, 25–36.PubMedPubMedCentral Qin, Y., Liu, H. J., Li, M., Zhai, D. H., Tang, Y. H., Yang, L., Qiao, K. L., Yang, J. H., Zhong, W. L., Zhang, Q., Liu, Y. R., Yang, G., Sun, T., & Yang, C. (2018). Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway. EBioMedicine, 38, 25–36.PubMedPubMedCentral
124.
go back to reference Spranger, S., Bao, R., & Gajewski, T. F. (2015). Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature, 523(7559), 231–235.PubMed Spranger, S., Bao, R., & Gajewski, T. F. (2015). Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature, 523(7559), 231–235.PubMed
125.
go back to reference Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017). Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell, 31(5), 711–723.e4.PubMedPubMedCentral Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017). Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell, 31(5), 711–723.e4.PubMedPubMedCentral
126.
go back to reference George, S., Miao, D., Demetri, G. D., Adeegbe, D., Rodig, S. J., Shukla, S., Lipschitz, M., Amin-Mansour, A., Raut, C. P., Carter, S. L., Hammerman, P., Freeman, G. J., Wu, C. J., Ott, P. A., Wong, K. K., & Van Allen, E. M. (2017). Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity, 46(2), 197–204.PubMedPubMedCentral George, S., Miao, D., Demetri, G. D., Adeegbe, D., Rodig, S. J., Shukla, S., Lipschitz, M., Amin-Mansour, A., Raut, C. P., Carter, S. L., Hammerman, P., Freeman, G. J., Wu, C. J., Ott, P. A., Wong, K. K., & Van Allen, E. M. (2017). Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity, 46(2), 197–204.PubMedPubMedCentral
127.
go back to reference Terry, S., Faouzi Zaarour, R., Hassan Venkatesh, G., Francis, A., El-Sayed, W., Buart, S., Bravo, P., Thiery, J., & Chouaib, S. (2018). Role of hypoxic stress in regulating tumor immunogenicity, resistance and plasticity. International Journal of Molecular Sciences, 19(10), 3044.PubMedPubMedCentral Terry, S., Faouzi Zaarour, R., Hassan Venkatesh, G., Francis, A., El-Sayed, W., Buart, S., Bravo, P., Thiery, J., & Chouaib, S. (2018). Role of hypoxic stress in regulating tumor immunogenicity, resistance and plasticity. International Journal of Molecular Sciences, 19(10), 3044.PubMedPubMedCentral
128.
go back to reference Malek, R., Wang, H., Taparra, K., & Tran, P. T. (2017). Therapeutic targeting of epithelial plasticity programs: focus on the epithelial-mesenchymal transition. Cells, Tissues, Organs, 203(2), 114–127.PubMed Malek, R., Wang, H., Taparra, K., & Tran, P. T. (2017). Therapeutic targeting of epithelial plasticity programs: focus on the epithelial-mesenchymal transition. Cells, Tissues, Organs, 203(2), 114–127.PubMed
129.
go back to reference Holmgaard, R. B., Schaer, D. A., Li, Y., Castaneda, S. P., Murphy, M. Y., Xu, X., Inigo, I., Dobkin, J., Manro, J. R., Iversen, P. W., Surguladze, D., Hall, G. E., Novosiadly, R. D., Benhadji, K. A., Plowman, G. D., Kalos, M., & Driscoll, K. E. (2018). Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade. Journal For Immunotherapy of Cancer, 6(1), 47.PubMedPubMedCentral Holmgaard, R. B., Schaer, D. A., Li, Y., Castaneda, S. P., Murphy, M. Y., Xu, X., Inigo, I., Dobkin, J., Manro, J. R., Iversen, P. W., Surguladze, D., Hall, G. E., Novosiadly, R. D., Benhadji, K. A., Plowman, G. D., Kalos, M., & Driscoll, K. E. (2018). Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade. Journal For Immunotherapy of Cancer, 6(1), 47.PubMedPubMedCentral
130.
go back to reference Sow, H. S., Ren, J., Camps, M., Ossendorp, F., & Ten Dijke, P. (2019). Combined inhibition of TGF-β signaling and the PD-L1 immune checkpoint is differentially effective in tumor models. Cells, 8(4), 320.PubMedPubMedCentral Sow, H. S., Ren, J., Camps, M., Ossendorp, F., & Ten Dijke, P. (2019). Combined inhibition of TGF-β signaling and the PD-L1 immune checkpoint is differentially effective in tumor models. Cells, 8(4), 320.PubMedPubMedCentral
131.
go back to reference Yang, Y., Xu, W., Peng, D., Wang, H., Zhang, X., Wang, H., Xiao, F., Zhu, Y., Ji, Y., Gulukota, K., Helseth, D. L., Jr., Mangold, K. A., Sullivan, M., Kaul, K., Wang, E., Prabhakar, B. S., Li, J., Wu, X., Wang, L., & Seth, P. (2019). An oncolytic adenovirus targeting transforming growth factor β inhibits protumorigenic signals and produces immune activation: A novel approach to enhance anti-PD-1 and anti-CTLA-4 therapy. Human gene therapy, 30(9), 1117–1132.PubMedPubMedCentral Yang, Y., Xu, W., Peng, D., Wang, H., Zhang, X., Wang, H., Xiao, F., Zhu, Y., Ji, Y., Gulukota, K., Helseth, D. L., Jr., Mangold, K. A., Sullivan, M., Kaul, K., Wang, E., Prabhakar, B. S., Li, J., Wu, X., Wang, L., & Seth, P. (2019). An oncolytic adenovirus targeting transforming growth factor β inhibits protumorigenic signals and produces immune activation: A novel approach to enhance anti-PD-1 and anti-CTLA-4 therapy. Human gene therapy, 30(9), 1117–1132.PubMedPubMedCentral
132.
go back to reference Dodagatta-Marri, E., Meyer, D. S., Reeves, M. Q., Paniagua, R., To, M. D., Binnewies, M., Broz, M. L., Mori, H., Wu, D., Adoumie, M., Del Rosario, R., Li, O., Buchmann, T., Liang, B., Malato, J., Arce Vargus, F., Sheppard, D., Hann, B. C., Mirza, A., et al. (2019). α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas. Journal for Immunotherapy of Cancer, 7(1), 62.PubMedPubMedCentral Dodagatta-Marri, E., Meyer, D. S., Reeves, M. Q., Paniagua, R., To, M. D., Binnewies, M., Broz, M. L., Mori, H., Wu, D., Adoumie, M., Del Rosario, R., Li, O., Buchmann, T., Liang, B., Malato, J., Arce Vargus, F., Sheppard, D., Hann, B. C., Mirza, A., et al. (2019). α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas. Journal for Immunotherapy of Cancer, 7(1), 62.PubMedPubMedCentral
133.
go back to reference Knudson, K. M., Hicks, K. C., Luo, X., Chen, J. Q., Schlom, J., & Gameiro, S. R. (2018). M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. Oncoimmunology, 7(5), e1426519.PubMedPubMedCentral Knudson, K. M., Hicks, K. C., Luo, X., Chen, J. Q., Schlom, J., & Gameiro, S. R. (2018). M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. Oncoimmunology, 7(5), e1426519.PubMedPubMedCentral
134.
go back to reference Lan, Y., Zhang, D., Xu, C., Hance, K. W., Marelli, B., Qi, J., Yu, H., Qin, G., Sircar, A., Hernández, V. M., Jenkins, M. H., Fontana, R. E., Deshpande, A., Locke, G., Sabzevari, H., Radvanyi, L., & Lo, K. M. (2018). Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β. Science Translational Medicine, 10(424), eaan5488.PubMed Lan, Y., Zhang, D., Xu, C., Hance, K. W., Marelli, B., Qi, J., Yu, H., Qin, G., Sircar, A., Hernández, V. M., Jenkins, M. H., Fontana, R. E., Deshpande, A., Locke, G., Sabzevari, H., Radvanyi, L., & Lo, K. M. (2018). Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β. Science Translational Medicine, 10(424), eaan5488.PubMed
135.
go back to reference Grenga, I., Donahue, R. N., Gargulak, M. L., Lepone, L. M., Roselli, M., Bilusic, M., & Schlom, J. (2018). Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis. Urologic Oncology, 36(3), 93.e1–93.e11.PubMed Grenga, I., Donahue, R. N., Gargulak, M. L., Lepone, L. M., Roselli, M., Bilusic, M., & Schlom, J. (2018). Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis. Urologic Oncology, 36(3), 93.e1–93.e11.PubMed
136.
go back to reference Strauss, J., Heery, C. R., Schlom, J., Madan, R. A., Cao, L., Kang, Z., Lamping, E., Marté, J. L., Donahue, R. N., Grenga, I., Cordes, L., Christensen, O., Mahnke, L., Helwig, C., & Gulley, J. L. (2018). Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors. Clinical Cancer Research, 24(6), 1287–1295.PubMedPubMedCentral Strauss, J., Heery, C. R., Schlom, J., Madan, R. A., Cao, L., Kang, Z., Lamping, E., Marté, J. L., Donahue, R. N., Grenga, I., Cordes, L., Christensen, O., Mahnke, L., Helwig, C., & Gulley, J. L. (2018). Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors. Clinical Cancer Research, 24(6), 1287–1295.PubMedPubMedCentral
137.
go back to reference Kang, S. H., Keam, B., Ahn, Y. O., Park, H. R., Kim, M., Kim, T. M., Kim, D. W., & Heo, D. S. (2018). Inhibition of MEK with trametinib enhances the efficacy of anti-PD-L1 inhibitor by regulating anti-tumor immunity in head and neck squamous cell carcinoma. Oncoimmunology, 8(1), e1515057.PubMedPubMedCentral Kang, S. H., Keam, B., Ahn, Y. O., Park, H. R., Kim, M., Kim, T. M., Kim, D. W., & Heo, D. S. (2018). Inhibition of MEK with trametinib enhances the efficacy of anti-PD-L1 inhibitor by regulating anti-tumor immunity in head and neck squamous cell carcinoma. Oncoimmunology, 8(1), e1515057.PubMedPubMedCentral
138.
go back to reference Hellmann, M. D., Kim, T. W., Lee, C. B., Goh, B. C., Miller, W. H., Jr., Oh, D. Y., Jamal, R., Chee, C. E., Chow, L. Q. M., Gainor, J. F., Desai, J., Solomon, B. J., Das Thakur, M., Pitcher, B., Foster, P., Hernandez, G., Wongchenko, M. J., Cha, E., Bang, Y. J., et al. (2019). Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Annals of Oncology, 30(7), 1134–1142.PubMedPubMedCentral Hellmann, M. D., Kim, T. W., Lee, C. B., Goh, B. C., Miller, W. H., Jr., Oh, D. Y., Jamal, R., Chee, C. E., Chow, L. Q. M., Gainor, J. F., Desai, J., Solomon, B. J., Das Thakur, M., Pitcher, B., Foster, P., Hernandez, G., Wongchenko, M. J., Cha, E., Bang, Y. J., et al. (2019). Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Annals of Oncology, 30(7), 1134–1142.PubMedPubMedCentral
139.
go back to reference Singh, D., Khan, M. A., & Siddique, H. R. (2020). Emerging role of long non-coding RNAs in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting. Molecular Biology Reports, 47(7), 5569–5585.PubMed Singh, D., Khan, M. A., & Siddique, H. R. (2020). Emerging role of long non-coding RNAs in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting. Molecular Biology Reports, 47(7), 5569–5585.PubMed
140.
go back to reference Singh, D., Kesharwani, P., Alhakamy, N. A., & Siddique, H. R. (2022). Accentuating CircRNA-miRNA-transcription factors axis: A conundrum in cancer research. Frontiers in Pharmacology, 12, 784801.PubMedPubMedCentral Singh, D., Kesharwani, P., Alhakamy, N. A., & Siddique, H. R. (2022). Accentuating CircRNA-miRNA-transcription factors axis: A conundrum in cancer research. Frontiers in Pharmacology, 12, 784801.PubMedPubMedCentral
141.
go back to reference Singh, D., Khan, M. A., & Siddique, H. R. (2023). Role of epigenetic drugs in sensitizing cancers to anticancer therapies: emerging trends and clinical advancements. Epigenomics, 15(8), 517–537.PubMed Singh, D., Khan, M. A., & Siddique, H. R. (2023). Role of epigenetic drugs in sensitizing cancers to anticancer therapies: emerging trends and clinical advancements. Epigenomics, 15(8), 517–537.PubMed
Metadata
Title
Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance
Authors
Deepti Singh
Hifzur R. Siddique
Publication date
30-09-2023
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 1/2024
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-023-10141-y

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