Top

11-05-2024 | Metastasis | Review

The roles of PD-L1 in the various stages of tumor metastasis

Authors: Yinjun He, Ming Zhu, Xuan Lai, Honghe Zhang, Weiqin Jiang

Published in: Cancer and Metastasis Reviews

Abstract

The interaction between tumor programmed death ligand 1 (PD-L1) and T-cell programmed cell death 1 (PD-1) has long been acknowledged as a mechanism for evading immune surveillance. Recent studies, however, have unveiled a more nuanced role of tumor-intrinsic PD-L1 in reprograming tumoral phenotypes. Preclinical models emphasize the synchronized effects of both intracellular and extracellular PD-L1 in promoting metastasis, with intricate interactions with the immune system. This review aims to summarize recent findings to elucidate the spatiotemporal heterogeneity of PD-L1 expression and the pro-metastatic roles of PD-L1 in the entire process of tumor metastasis. For example, PD-L1 regulates the epithelial-to-mesenchymal transition (EMT) process, facilitates the survival of circulating tumor cells, and induces the formation of immunosuppressive environments at pre-metastatic niches and metastatic sites. And the complexed and dynamic regulation process of PD-L1 for tumor metastasis is related to the spatiotemporal heterogeneity of PD-L1 expression and functions from tumor primary sites to various metastatic sites. This review extends the current understandings for the roles of PD-L1 in mediating tumor metastasis and provides new insights into therapeutic decisions in clinical practice.

Chen, L., & Han, X. (2015). Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. The Journal of Clinical Investigation, 125(9), 3384–3391. https://doi.org/10.1172/JCI80011CrossRefPubMedPubMedCentral

Pauken, K. E., & Wherry, E. J. (2015). Overcoming T cell exhaustion in infection and cancer. Trends in Immunology, 36(4), 265–276. https://doi.org/10.1016/j.it.2015.02.008CrossRefPubMedPubMedCentral

Kornepati, A. V. R., Vadlamudi, R. K., & Curiel, T. J. (2022). Programmed death ligand 1 signals in cancer cells. Nature Reviews. Cancer, 22(3), 174–189. https://doi.org/10.1038/s41568-021-00431-4CrossRefPubMedPubMedCentral

Hanks, B. A. (2022). The “Inside” Story on Tumor-Expressed PD-L1. Cancer Research, 82(11), 2069–2071. https://doi.org/10.1158/0008-5472.CAN-22-1060CrossRefPubMedPubMedCentral

Kornepati, A. V. R., Boyd, J. T., Murray, C. E., Saifetiarova, J., de la Peña Avalos, B., Rogers, C. M., et al. (2022). Tumor Intrinsic PD-L1 Promotes DNA Repair in Distinct Cancers and Suppresses PARP Inhibitor-Induced Synthetic Lethality. Cancer Research, 82(11), 2156–2170. https://doi.org/10.1158/0008-5472.CAN-21-2076CrossRefPubMedPubMedCentral

Tu, X., Qin, B., Zhang, Y., Zhang, C., Kahila, M., Nowsheen, S., et al. (2019). PD-L1 (B7-H1) Competes with the RNA Exosome to Regulate the DNA Damage Response and Can Be Targeted to Sensitize to Radiation or Chemotherapy. Molecular Cell, 74(6), 1215–1226.e4. https://doi.org/10.1016/j.molcel.2019.04.005CrossRefPubMedPubMedCentral

Clark, C. A., Gupta, H. B., Sareddy, G., Pandeswara, S., Lao, S., Yuan, B., et al. (2016). Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma. Cancer Research, 76(23), 6964–6974. https://doi.org/10.1158/0008-5472.CAN-16-0258CrossRefPubMedPubMedCentral

Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., et al. (2015). Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell, 162(6), 1229–1241. https://doi.org/10.1016/j.cell.2015.08.016CrossRefPubMedPubMedCentral

Alsuliman, A., Colak, D., Al-Harazi, O., Fitwi, H., Tulbah, A., Al-Tweigeri, T., et al. (2015). Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: significance in claudin-low breast cancer cells. Molecular Cancer, 14, 149. https://doi.org/10.1186/s12943-015-0421-2CrossRefPubMedPubMedCentral

10.

Chen, C., Li, S., Xue, J., Qi, M., Liu, X., Huang, Y., et al. (2021). PD-L1 tumor-intrinsic signaling and its therapeutic implication in triple-negative breast cancer. JCI Insight, 6(8), 131458. https://doi.org/10.1172/jci.insight.131458CrossRefPubMed

11.

Nieto, C., Miller, B., Alzofon, N., Chimed, T., Himes, J., Joshi, M., et al. (2023). The PD-L1 interactome demonstrates bidirectional signaling coordinating immune suppression and cancer progression in HNSCC. Journal of the National Cancer Institute, djad126. https://doi.org/10.1093/jnci/djad126

12.

Xu, Y., Poggio, M., Jin, H. Y., Shi, Z., Forester, C. M., Wang, Y., et al. (2019). Translation control of the immune checkpoint in cancer and its therapeutic targeting. Nature Medicine, 25(2), 301–311. https://doi.org/10.1038/s41591-018-0321-2CrossRefPubMedPubMedCentral

13.

Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y.-H., Byers, L. A., 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. https://doi.org/10.1038/ncomms6241CrossRefPubMed

14.

Xie, M., Lin, Z., Ji, X., Luo, X., Zhang, Z., Sun, M., et al. (2023). FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. Journal of Hepatology, 79(1), 109–125. https://doi.org/10.1016/j.jhep.2023.02.036CrossRefPubMed

15.

Ghosh, S., Nataraj, N. B., Noronha, A., Patkar, S., Sekar, A., Mukherjee, S., et al. (2021). PD-L1 recruits phospholipase C and enhances tumorigenicity of lung tumors harboring mutant forms of EGFR. Cell Reports, 35(8), 109181. https://doi.org/10.1016/j.celrep.2021.109181CrossRefPubMed

16.

Jiang, Y., & Zhan, H. (2020). Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion. Cancer Letters, 468, 72–81. https://doi.org/10.1016/j.canlet.2019.10.013CrossRefPubMed

17.

Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J.-J., Rutkowski, P., Lao, C. D., et al. (2019). Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. The New England Journal of Medicine, 381(16), 1535–1546. https://doi.org/10.1056/NEJMoa1910836CrossRefPubMed

18.

Schmid, P., Cortes, J., Pusztai, L., McArthur, H., Kümmel, S., Bergh, J., et al. (2020). Pembrolizumab for Early Triple-Negative Breast Cancer. The New England Journal of Medicine, 382(9), 810–821. https://doi.org/10.1056/NEJMoa1910549CrossRefPubMed

19.

Forde, P. M., Chaft, J. E., Smith, K. N., Anagnostou, V., Cottrell, T. R., Hellmann, M. D., et al. (2018). Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. The New England Journal of Medicine, 378(21), 1976–1986. https://doi.org/10.1056/NEJMoa1716078CrossRefPubMedPubMedCentral

20.

Cercek, A., Roxburgh, C. S. D., Strombom, P., Smith, J. J., Temple, L. K. F., Nash, G. M., et al. (2018). Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA oncology, 4(6), e180071. https://doi.org/10.1001/jamaoncol.2018.0071CrossRefPubMedPubMedCentral

21.

Eggermont, A. M. M., Blank, C. U., Mandalà, M., Long, G. V., Atkinson, V. G., Dalle, S., et al. (2021). Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. The Lancet. Oncology, 22(5), 643–654. https://doi.org/10.1016/S1470-2045(21)00065-6CrossRefPubMed

22.

Gerstberger, S., Jiang, Q., & Ganesh, K. (2023). Metastasis. Cell, 186(8), 1564–1579. https://doi.org/10.1016/j.cell.2023.03.003CrossRefPubMedPubMedCentral

23.

Zou, Y., Hu, X., Zheng, S., Yang, A., Li, X., Tang, H., et al. (2021). Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis. EBioMedicine, 63, 103137. https://doi.org/10.1016/j.ebiom.2020.103137CrossRefPubMed

24.

Torborg, S. R., Li, Z., Chan, J. E., & Tammela, T. (2022). Cellular and molecular mechanisms of plasticity in cancer. Trends in Cancer, 8(9), 735–746. https://doi.org/10.1016/j.trecan.2022.04.007CrossRefPubMedPubMedCentral

25.

Pérez-González, A., Bévant, K., & Blanpain, C. (2023). Cancer cell plasticity during tumor progression, metastasis and response to therapy. Nature Cancer, 4(8), 1063–1082. https://doi.org/10.1038/s43018-023-00595-yCrossRefPubMedPubMedCentral

26.

Yuan, S., Norgard, R. J., & Stanger, B. Z. (2019). Cellular Plasticity in Cancer. Cancer Discovery, 9(7), 837–851. https://doi.org/10.1158/2159-8290.CD-19-0015CrossRefPubMedPubMedCentral

27.

Hanahan, D. (2022). Hallmarks of Cancer: New Dimensions. Cancer Discovery, 12(1), 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059CrossRefPubMed

28.

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. https://doi.org/10.1038/nrclinonc.2017.44CrossRefPubMedPubMedCentral

29.

Del Pozo Martin, Y., Park, D., Ramachandran, A., Ombrato, L., Calvo, F., Chakravarty, P., et al. (2015). Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization. Cell Reports, 13(11), 2456–2469. https://doi.org/10.1016/j.celrep.2015.11.025CrossRefPubMed

30.

Liu, M., Wang, R., Sun, X., Liu, Y., Wang, Z., Yan, J., et al. (2020). Prognostic significance of PD-L1 expression on cell-surface vimentin-positive circulating tumor cells in gastric cancer patients. Molecular Oncology, 14(4), 865–881. https://doi.org/10.1002/1878-0261.12643CrossRefPubMedPubMedCentral

31.

Kim, S., Koh, J., Kim, M.-Y., Kwon, D., Go, H., Kim, Y. A., et al. (2016). PD-L1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung. Human Pathology, 58, 7–14. https://doi.org/10.1016/j.humpath.2016.07.007CrossRefPubMed

32.

Lou, Y., Diao, L., Cuentas, E. R. P., Denning, W. L., Chen, L., Fan, Y. H., et al. (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: An Official Journal of the American Association for Cancer Research, 22(14), 3630–3642. https://doi.org/10.1158/1078-0432.CCR-15-1434CrossRefPubMed

33.

Qiu, X. Y., Hu, D. X., Chen, W.-Q., Chen, R. Q., Qian, S. R., Li, C. Y., et al. (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. https://doi.org/10.1016/j.bbadis.2018.03.002CrossRefPubMed

34.

Yu, W., Hua, Y., Qiu, H., Hao, J., Zou, K., Li, Z., et al. (2020). PD-L1 promotes tumor growth and progression by activating WIP and β-catenin signaling pathways and predicts poor prognosis in lung cancer. Cell Death & Disease, 11(7), 506. https://doi.org/10.1038/s41419-020-2701-zCrossRef

35.

Wang, S., Li, J., Xie, J., Liu, F., Duan, Y., Wu, Y., et al. (2018). Programmed death ligand 1 promotes lymph node metastasis and glucose metabolism in cervical cancer by activating integrin β4/SNAI1/SIRT3 signaling pathway. Oncogene, 37(30), 4164–4180. https://doi.org/10.1038/s41388-018-0252-xCrossRefPubMed

36.

Tsutsumi, S., Saeki, H., Nakashima, Y., Ito, S., Oki, E., Morita, M., et al. (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. https://doi.org/10.1111/cas.13237CrossRefPubMedPubMedCentral

37.

Kong, X., Peng, H., Liu, P., Fu, X., Wang, N., & Zhang, D. (2023). Programmed death ligand 1 regulates epithelial-mesenchymal transition and cancer stem cell phenotypes in hepatocellular carcinoma through the serum and glucocorticoid kinase 2/β-catenin signaling pathway. Cancer Science, 114(6), 2265–2276. https://doi.org/10.1111/cas.15753CrossRefPubMedPubMedCentral

38.

Fei, Z., Deng, Z., Zhou, L., Li, K., Xia, X., & Xie, R. (2019). PD-L1 Induces Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway. Oncology Research, 27(7), 801–807. https://doi.org/10.3727/096504018X15446984186056CrossRefPubMedPubMedCentral

39.

Ishaque, N., Abba, M. L., Hauser, C., Patil, N., Paramasivam, N., Huebschmann, D., et al. (2018). Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. Nature Communications, 9(1), 4782. https://doi.org/10.1038/s41467-018-07041-zCrossRefPubMedPubMedCentral

40.

Cui, B., Chen, J., Luo, M., Liu, Y., Chen, H., Lü, D., et al. (2021). PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling. International Journal of Oral Science, 13(1), 8. https://doi.org/10.1038/s41368-021-00112-wCrossRefPubMedPubMedCentral

41.

Noman, M. Z., Janji, B., Abdou, A., Hasmim, M., Terry, S., Tan, T. Z., et al. (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. https://doi.org/10.1080/2162402X.2016.1263412CrossRefPubMedPubMedCentral

42.

Cha, J.-H., Chan, L.-C., Li, C.-W., Hsu, J. L., & Hung, M.-C. (2019). Mechanisms Controlling PD-L1 Expression in Cancer. Molecular Cell, 76(3), 359–370. https://doi.org/10.1016/j.molcel.2019.09.030CrossRefPubMedPubMedCentral

43.

Wei, Y., Zhao, Q., Gao, Z., Lao, X.-M., Lin, W.-M., Chen, D.-P., et al. (2019). The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy. The Journal of Clinical Investigation, 129(8), 3347–3360. https://doi.org/10.1172/JCI127726CrossRefPubMedPubMedCentral

44.

Augustin, R. C., Newman, S., Li, A., Joy, M., Lyons, M., Pham, M. P., et al. (2023). Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma. Journal for Immunotherapy of Cancer, 11(10), e007567. https://doi.org/10.1136/jitc-2023-007567CrossRefPubMedPubMedCentral

45.

Moutafi, M. K., Tao, W., Huang, R., Haberberger, J., Alexander, B., Ramkissoon, S., et al. (2021). Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer. Journal for Immunotherapy of Cancer, 9(4), e002230. https://doi.org/10.1136/jitc-2020-002230CrossRefPubMedPubMedCentral

46.

Yoon, H. H., Jin, Z., Kour, O., Kankeu Fonkoua, L. A., Shitara, K., Gibson, M. K., et al. (2022). Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer: Systematic Review and Meta-analysis of 17 Phase 3 Randomized Clinical Trials. JAMA Oncology, 8(10), 1456–1465. https://doi.org/10.1001/jamaoncol.2022.3707CrossRefPubMedPubMedCentral

47.

Reticker-Flynn, N. E., Zhang, W., Belk, J. A., Basto, P. A., Escalante, N. K., Pilarowski, G. O. W., et al. (2022). Lymph node colonization induces tumor-immune tolerance to promote distant metastasis. Cell, 185(11), 1924–1942.e23. https://doi.org/10.1016/j.cell.2022.04.019CrossRefPubMedPubMedCentral

48.

Kleffel, S., Posch, C., Barthel, S. R., Mueller, H., Schlapbach, C., Guenova, E., et al. (2015). Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell, 162(6), 1242–1256. https://doi.org/10.1016/j.cell.2015.08.052CrossRefPubMedPubMedCentral

49.

Wu, R.-Y., Kong, P.-F., Xia, L.-P., Huang, Y., Li, Z.-L., Tang, Y.-Y., et al. (2019). Regorafenib Promotes Antitumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 25(14), 4530–4541. https://doi.org/10.1158/1078-0432.CCR-18-2840CrossRefPubMed

50.

Klement, J. D., Redd, P. S., Lu, C., Merting, A. D., Poschel, D. B., Yang, D., et al. (2023). Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment. Cancer Cell, 41(3), 620–636.e9. https://doi.org/10.1016/j.ccell.2023.02.005CrossRefPubMedPubMedCentral

51.

Liu, C.-Q., Xu, J., Zhou, Z.-G., Jin, L.-L., Yu, X.-J., Xiao, G., et al. (2018). Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma. British Journal of Cancer, 119(1), 80–88. https://doi.org/10.1038/s41416-018-0144-4CrossRefPubMedPubMedCentral

52.

Noguchi, T., Ward, J. P., Gubin, M. M., Arthur, C. D., Lee, S. H., Hundal, J., et al. (2017). Temporally Distinct PD-L1 Expression by Tumor and Host Cells Contributes to Immune Escape. Cancer Immunology Research, 5(2), 106–117. https://doi.org/10.1158/2326-6066.CIR-16-0391CrossRefPubMedPubMedCentral

53.

Petty, A. J., Dai, R., Lapalombella, R., Baiocchi, R. A., Benson, D. M., Li, Z., et al. (2021). Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function. JCI Insight, 6(6), 146707. https://doi.org/10.1172/jci.insight.146707CrossRefPubMed

54.

Oh, S. A., Wu, D.-C., Cheung, J., Navarro, A., Xiong, H., Cubas, R., et al. (2020). PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer. Nature Cancer, 1(7), 681–691. https://doi.org/10.1038/s43018-020-0075-xCrossRefPubMed

55.

Zhang, Y., Velez-Delgado, A., Mathew, E., Li, D., Mendez, F. M., Flannagan, K., et al. (2017). Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut, 66(1), 124–136. https://doi.org/10.1136/gutjnl-2016-312078CrossRefPubMed

56.

Kuang, D.-M., Zhao, Q., Peng, C., Xu, J., Zhang, J.-P., Wu, C., & Zheng, L. (2009). Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. The Journal of Experimental Medicine, 206(6), 1327–1337. https://doi.org/10.1084/jem.20082173CrossRefPubMedPubMedCentral

57.

Mazel, M., Jacot, W., Pantel, K., Bartkowiak, K., Topart, D., Cayrefourcq, L., et al. (2015). Frequent expression of PD-L1 on circulating breast cancer cells. Molecular Oncology, 9(9), 1773–1782. https://doi.org/10.1016/j.molonc.2015.05.009CrossRefPubMedPubMedCentral

58.

Ilié, M., Szafer-Glusman, E., Hofman, V., Chamorey, E., Lalvée, S., Selva, E., et al. (2018). Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 29(1), 193–199. https://doi.org/10.1093/annonc/mdx636CrossRefPubMed

59.

Dall’Olio, F. G., Gelsomino, F., Conci, N., Marcolin, L., De Giglio, A., Grilli, G., et al. (2021). PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non-small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors. Clinical Lung Cancer, 22(5), 423–431. https://doi.org/10.1016/j.cllc.2021.03.005CrossRefPubMed

60.

Jacot, W., Mazel, M., Mollevi, C., Pouderoux, S., D’Hondt, V., Cayrefourcq, L., et al. (2020). Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer. Clinical Chemistry, 66(8), 1093–1101. https://doi.org/10.1093/clinchem/hvaa121CrossRefPubMed

61.

Bergmann, S., Coym, A., Ott, L., Soave, A., Rink, M., Janning, M., et al. (2020). Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC). Oncoimmunology, 9(1), 1738798. https://doi.org/10.1080/2162402X.2020.1738798CrossRefPubMedPubMedCentral

62.

Winograd, P., Hou, S., Court, C. M., Lee, Y.-T., Chen, P.-J., Zhu, Y., et al. (2020). Hepatocellular Carcinoma-Circulating Tumor Cells Expressing PD-L1 Are Prognostic and Potentially Associated With Response to Checkpoint Inhibitors. Hepatology Communications, 4(10), 1527–1540. https://doi.org/10.1002/hep4.1577CrossRefPubMedPubMedCentral

63.

Bootsma, M., McKay, R. R., Emamekhoo, H., Bade, R. M., Schehr, J. L., Mannino, M. C., et al. (2022). Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 40(31), 3633–3641. https://doi.org/10.1200/JCO.22.00219CrossRefPubMed

64.

Strati, A., Koutsodontis, G., Papaxoinis, G., Angelidis, I., Zavridou, M., Economopoulou, P., et al. (2017). Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 28(8), 1923–1933. https://doi.org/10.1093/annonc/mdx206CrossRefPubMed

65.

Flores-Guzmán, F., Utikal, J., & Umansky, V. (2020). Dormant tumor cells interact with memory CD8+ T cells in RET transgenic mouse melanoma model. Cancer Letters, 474, 74–81. https://doi.org/10.1016/j.canlet.2020.01.016CrossRefPubMed

66.

Naxerova, K., Reiter, J. G., Brachtel, E., Lennerz, J. K., van de Wetering, M., Rowan, A., et al. (2017). Origins of lymphatic and distant metastases in human colorectal cancer. Science (New York, N.Y.), 357(6346), 55–60. https://doi.org/10.1126/science.aai8515CrossRefPubMed

67.

Wang, R., Li, J., Zhou, X., Mao, Y., Wang, W., Gao, S., et al. (2022). Single-cell genomic and transcriptomic landscapes of primary and metastatic colorectal cancer tumors. Genome Medicine, 14(1), 93. https://doi.org/10.1186/s13073-022-01093-zCrossRefPubMedPubMedCentral

68.

Reiter, J. G., Hung, W.-T., Lee, I.-H., Nagpal, S., Giunta, P., Degner, S., et al. (2020). Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases. Nature Genetics, 52(7), 692–700. https://doi.org/10.1038/s41588-020-0633-2CrossRefPubMedPubMedCentral

69.

Mk, R., Tlh, O., Kb, J., Ee, M., Cc, L., Jl, Y., et al. (2023). Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell, 186(6). https://doi.org/10.1016/j.cell.2023.02.021

70.

Dammeijer, F., van Gulijk, M., Mulder, E. E., Lukkes, M., Klaase, L., van den Bosch, T., et al. (2020). The PD-1/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes. Cancer Cell, 38(5), 685–700.e8. https://doi.org/10.1016/j.ccell.2020.09.001CrossRefPubMed

71.

van Krimpen, A., Gerretsen, V. I. V., Mulder, E. E. A. P., van Gulijk, M., van den Bosch, T. P. P., von der Thüsen, J., et al. (2022). Immune suppression in the tumor-draining lymph node corresponds with distant disease recurrence in patients with melanoma. Cancer Cell, 40(8), 798–799. https://doi.org/10.1016/j.ccell.2022.06.009CrossRefPubMed

72.

Pylaeva, E., Korschunow, G., Spyra, I., Bordbari, S., Siakaeva, E., Ozel, I., et al. (2022). During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes. Cell Reports, 40(7). https://doi.org/10.1016/j.celrep.2022.111171

73.

Cousin, N., Cap, S., Dihr, M., Tacconi, C., Detmar, M., & Dieterich, L. C. (2021). Lymphatic PD-L1 Expression Restricts Tumor-Specific CD8+ T-cell Responses. Cancer Research, 81(15), 4133–4144. https://doi.org/10.1158/0008-5472.CAN-21-0633CrossRefPubMedPubMedCentral

74.

Patras, L., Shaashua, L., Matei, I., & Lyden, D. (2023). Immune determinants of the pre-metastatic niche. Cancer Cell, 41(3), 546–572. https://doi.org/10.1016/j.ccell.2023.02.018CrossRefPubMedPubMedCentral

75.

Guo, Y., Ji, X., Liu, J., Fan, D., Zhou, Q., Chen, C., et al. (2019). Effects of exosomes on pre-metastatic niche formation in tumors. Molecular Cancer, 18(1), 39. https://doi.org/10.1186/s12943-019-0995-1CrossRefPubMedPubMedCentral

76.

Poggio, M., Hu, T., Pai, C.-C., Chu, B., Belair, C. D., Chang, A., et al. (2019). Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory. Cell, 177(2), 414–427.e13. https://doi.org/10.1016/j.cell.2019.02.016CrossRefPubMedPubMedCentral

77.

Chen, G., Huang, A. C., Zhang, W., Zhang, G., Wu, M., Xu, W., et al. (2018). Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature, 560(7718), 382–386. https://doi.org/10.1038/s41586-018-0392-8CrossRefPubMedPubMedCentral

78.

Wang, J., Zhang, H., Sun, X., Wang, X., Ren, T., Huang, Y., et al. (2020). Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients. Journal of Nanobiotechnology, 18(1), 151. https://doi.org/10.1186/s12951-020-00710-6CrossRefPubMedPubMedCentral

79.

Sun, Y., Guo, J., Yu, L., Guo, T., Wang, J., Wang, X., & Chen, Y. (2021). PD-L1+ exosomes from bone marrow-derived cells of tumor-bearing mice inhibit antitumor immunity. Cellular & Molecular Immunology, 18(10), 2402–2409. https://doi.org/10.1038/s41423-020-0487-7CrossRef

80.

Chen, J., Song, Y., Miao, F., Chen, G., Zhu, Y., Wu, N., et al. (2021). PDL1-positive exosomes suppress antitumor immunity by inducing tumor-specific CD8+ T cell exhaustion during metastasis. Cancer Science, 112(9), 3437–3454. https://doi.org/10.1111/cas.15033CrossRefPubMedPubMedCentral

81.

Morrissey, S. M., Zhang, F., Ding, C., Montoya-Durango, D. E., Hu, X., Yang, C., et al. (2021). Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming. Cell Metabolism, 33(10), 2040–2058.e10. https://doi.org/10.1016/j.cmet.2021.09.002CrossRefPubMedPubMedCentral

82.

Hu, M., Kenific, C. M., Boudreau, N., & Lyden, D. (2023). Tumor-derived nanoseeds condition the soil for metastatic organotropism. Seminars in Cancer Biology, 93, 70–82. https://doi.org/10.1016/j.semcancer.2023.05.003CrossRefPubMed

83.

Zhang, W., Zhong, W., Wang, B., Yang, J., Yang, J., Yu, Z., et al. (2022). ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression. Developmental Cell, 57(3), 329–343.e7. https://doi.org/10.1016/j.devcel.2022.01.002CrossRefPubMedPubMedCentral

84.

Massagué, J., & Ganesh, K. (2021). Metastasis-Initiating Cells and Ecosystems. Cancer. Discovery, 11(4), 971–994. https://doi.org/10.1158/2159-8290.CD-21-0010CrossRef

85.

Guldner, I. H., Wang, Q., Yang, L., Golomb, S. M., Zhao, Z., Lopez, J. A., et al. (2020). CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10. Cell, 183(5), 1234–1248.e25. https://doi.org/10.1016/j.cell.2020.09.064CrossRefPubMedPubMedCentral

86.

Wang, X., Chen, Y., Lan, B., Wang, Y., Lin, W., Jiang, X., et al. (2022). Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells. Theranostics, 12(5), 2063–2079. https://doi.org/10.7150/thno.69198CrossRefPubMedPubMedCentral

87.

Wang, X., Hu, L.-P., Qin, W.-T., Yang, Q., Chen, D.-Y., Li, Q., et al. (2021). Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis. Nature Communications, 12(1), 174. https://doi.org/10.1038/s41467-020-20447-yCrossRefPubMedPubMedCentral

88.

Erlmeier, F., Klümper, N., Landgraf, L., Strissel, P. L., Strick, R., Sikic, D., et al. (2023). Spatial Immunephenotypes of Distant Metastases but not Matched Primary Urothelial Carcinomas Predict Response to Immune Checkpoint Inhibition. European Urology, 83(2), 133–142. https://doi.org/10.1016/j.eururo.2022.10.020CrossRefPubMed

89.

Mansfield, A. S., Aubry, M. C., Moser, J. C., Harrington, S. M., Dronca, R. S., Park, S. S., & Dong, H. (2016). Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 27(10), 1953–1958. https://doi.org/10.1093/annonc/mdw289CrossRefPubMed

90.

Kim, S., Koh, J., Kwon, D., Keam, B., Go, H., Kim, Y. A., et al. (2017). Comparative analysis of PD-L1 expression between primary and metastatic pulmonary adenocarcinomas. European Journal of Cancer (Oxford, England: 1990), 75, 141–149. https://doi.org/10.1016/j.ejca.2017.01.004CrossRefPubMed

91.

Schoenfeld, A. J., Rizvi, H., Bandlamudi, C., Sauter, J. L., Travis, W. D., Rekhtman, N., et al. (2020). Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 31(5), 599–608. https://doi.org/10.1016/j.annonc.2020.01.065CrossRefPubMed

92.

Rozenblit, M., Huang, R., Danziger, N., Hegde, P., Alexander, B., Ramkissoon, S., et al. (2020). Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal for Immunotherapy of Cancer, 8(2), e001558. https://doi.org/10.1136/jitc-2020-001558CrossRefPubMedPubMedCentral

93.

Szekely, B., Bossuyt, V., Li, X., Wali, V. B., Patwardhan, G. A., Frederick, C., et al. (2018). Immunological differences between primary and metastatic breast cancer. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 29(11), 2232–2239. https://doi.org/10.1093/annonc/mdy399CrossRefPubMed

94.

Restle, D., Dux, J., Li, X., Byun, A. J., Choe, J. K., Li, Y., et al. (2023). Organ-specific heterogeneity in tumor-infiltrating immune cells and cancer antigen expression in primary and autologous metastatic lung adenocarcinoma. Journal for Immunotherapy of Cancer, 11(6), e006609. https://doi.org/10.1136/jitc-2022-006609CrossRefPubMedPubMedCentral

95.

Callea, M., Albiges, L., Gupta, M., Cheng, S.-C., Genega, E. M., Fay, A. P., et al. (2015). Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma. Cancer Immunology Research, 3(10), 1158–1164. https://doi.org/10.1158/2326-6066.CIR-15-0043CrossRefPubMedPubMedCentral

96.

Parvathareddy, S. K., Siraj, A. K., Al-Badawi, I. A., Tulbah, A., Al-Dayel, F., & Al-Kuraya, K. S. (2021). Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation. Scientific Reports, 11(1), 3750. https://doi.org/10.1038/s41598-021-83276-zCrossRefPubMedPubMedCentral

97.

Hong, L., Negrao, M. V., Dibaj, S. S., Chen, R., Reuben, A., Bohac, J. M., et al. (2020). Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer, 15(9), 1449–1459. https://doi.org/10.1016/j.jtho.2020.04.026CrossRefPubMed

98.

García-Mulero, S., Alonso, M. H., Pardo, J., Santos, C., Sanjuan, X., Salazar, R., et al. (2020). Lung metastases share common immune features regardless of primary tumor origin. Journal for Immunotherapy of Cancer, 8(1), e000491. https://doi.org/10.1136/jitc-2019-000491CrossRefPubMedPubMedCentral

99.

Wu, J., Sun, W., Yang, X., Wang, H., Liu, X., Chi, K., et al. (2022). Heterogeneity of programmed death-ligand 1 expression and infiltrating lymphocytes in paired resected primary and metastatic non-small cell lung cancer. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 35(2), 218–227. https://doi.org/10.1038/s41379-021-00903-wCrossRefPubMed

100.

Placke, J.-M., Kimmig, M., Griewank, K., Herbst, R., Terheyden, P., Utikal, J., et al. (2023). Correlation of tumor PD-L1 expression in different tissue types and outcome of PD-1-based immunotherapy in metastatic melanoma - analysis of the DeCOG prospective multicenter cohort study ADOREG/TRIM. EBioMedicine, 96, 104774. https://doi.org/10.1016/j.ebiom.2023.104774CrossRefPubMedPubMedCentral

101.

Van den Eynde, M., Mlecnik, B., Bindea, G., Fredriksen, T., Church, S. E., Lafontaine, L., et al. (2018). The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients. Cancer Cell, 34(6), 1012–1026.e3. https://doi.org/10.1016/j.ccell.2018.11.003CrossRefPubMed

102.

Wang, X., Bai, H., Zhang, J., Wang, Z., Duan, J., Cai, H., et al. (2023). Genetic Intratumor Heterogeneity Remodels the Immune Microenvironment and Induces Immune Evasion in Brain Metastasis of Lung Cancer. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer, S1556-0864(23), 01079–01071. https://doi.org/10.1016/j.jtho.2023.09.276CrossRef

Title: The roles of PD-L1 in the various stages of tumor metastasis
Authors: Yinjun He
Ming Zhu
Xuan Lai
Honghe Zhang
Weiqin Jiang
Publication date: 11-05-2024
Publisher: Springer US
Keyword: Metastasis
Published in: Cancer and Metastasis Reviews
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-024-10189-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Keynote webinar | Spotlight on antibody–drug conjugates in cancer