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Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Review

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

Authors: Ming Yi, Dechao Jiao, Hanxiao Xu, Qian Liu, Weiheng Zhao, Xinwei Han, Kongming Wu

Published in: Molecular Cancer | Issue 1/2018

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Abstract

Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.
Literature
2.
3.
go back to reference Yu S, Liu Q, Han X, Qin S, Zhao W, Li A, et al. Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment. Exp Hematol Oncol. 2017;6:31.PubMedPubMedCentralCrossRef Yu S, Liu Q, Han X, Qin S, Zhao W, Li A, et al. Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment. Exp Hematol Oncol. 2017;6:31.PubMedPubMedCentralCrossRef
4.
go back to reference Crist M, Balar A. Atezolizumab in invasive and metastatic urothelial carcinoma. Expert Rev Clin Pharmacol. 2017;10:1295–301.PubMedCrossRef Crist M, Balar A. Atezolizumab in invasive and metastatic urothelial carcinoma. Expert Rev Clin Pharmacol. 2017;10:1295–301.PubMedCrossRef
5.
7.
go back to reference Patsoukis N, Brown J, Petkova V, Liu F, Li L, Boussiotis VA. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation. Sci Signal. 2012;5 ra46 Patsoukis N, Brown J, Petkova V, Liu F, Li L, Boussiotis VA. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation. Sci Signal. 2012;5 ra46
10.
go back to reference Kuol N, Stojanovska L, Nurgali K, Apostolopoulos V. PD-1/PD-L1 in disease. Immunotherapy. 2018;10:149–60.PubMedCrossRef Kuol N, Stojanovska L, Nurgali K, Apostolopoulos V. PD-1/PD-L1 in disease. Immunotherapy. 2018;10:149–60.PubMedCrossRef
11.
go back to reference Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, et al. PD-L1 prevents the development of autoimmune heart disease in graft-versus-host disease. J Immunol. 2018;200:834–46.PubMedCrossRef Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, et al. PD-L1 prevents the development of autoimmune heart disease in graft-versus-host disease. J Immunol. 2018;200:834–46.PubMedCrossRef
12.
go back to reference Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553:91–5.PubMedCrossRef Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553:91–5.PubMedCrossRef
14.
go back to reference Witt DA, Donson AM, Amani V, Moreira DC, Sanford B, Hoffman LM, et al. Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: implications for PD-1-targeted therapy. Pediatr Blood Cancer. 2018;65:e26960.PubMedCrossRef Witt DA, Donson AM, Amani V, Moreira DC, Sanford B, Hoffman LM, et al. Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: implications for PD-1-targeted therapy. Pediatr Blood Cancer. 2018;65:e26960.PubMedCrossRef
15.
go back to reference Zheng B, Ren T, Huang Y, Sun K, Wang S, Bao X, et al. PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse. J Hematol Oncol. 2018;11:16.PubMedPubMedCentralCrossRef Zheng B, Ren T, Huang Y, Sun K, Wang S, Bao X, et al. PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse. J Hematol Oncol. 2018;11:16.PubMedPubMedCentralCrossRef
16.
go back to reference Xu-Monette ZY, Zhang M, Li J, Young KH. PD-1/PD-L1 blockade: have we found the key to unleash the antitumor immune response? Front Immunol. 2017;8:1597.PubMedPubMedCentralCrossRef Xu-Monette ZY, Zhang M, Li J, Young KH. PD-1/PD-L1 blockade: have we found the key to unleash the antitumor immune response? Front Immunol. 2017;8:1597.PubMedPubMedCentralCrossRef
17.
go back to reference Karlsson AK, Saleh SN. Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis. Clin Cosmet Investig Dermatol. 2017;10:325–39.PubMedPubMedCentralCrossRef Karlsson AK, Saleh SN. Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis. Clin Cosmet Investig Dermatol. 2017;10:325–39.PubMedPubMedCentralCrossRef
18.
19.
go back to reference Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for Cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.PubMedPubMedCentralCrossRef Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for Cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.PubMedPubMedCentralCrossRef
22.
go back to reference Polk A, Svane IM, Andersson M, Nielsen D. Checkpoint inhibitors in breast cancer - current status. Cancer Treat Rev. 2017;63:122–34.PubMedCrossRef Polk A, Svane IM, Andersson M, Nielsen D. Checkpoint inhibitors in breast cancer - current status. Cancer Treat Rev. 2017;63:122–34.PubMedCrossRef
23.
go back to reference Sheng Z, Zhu X, Sun Y, Zhang Y. The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. Oncotarget. 2017;8:57826–35.PubMedPubMedCentral Sheng Z, Zhu X, Sun Y, Zhang Y. The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. Oncotarget. 2017;8:57826–35.PubMedPubMedCentral
24.
go back to reference Ancevski Hunter K, Socinski MA, Villaruz LC. PD-L1 testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in lung Cancer. Mol Diagn Ther. 2018;22:1–10.PubMedCrossRef Ancevski Hunter K, Socinski MA, Villaruz LC. PD-L1 testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in lung Cancer. Mol Diagn Ther. 2018;22:1–10.PubMedCrossRef
25.
go back to reference Janjigian YY, Sanchez-Vega F, Jonsson P, Chatila WK, Hechtman JF, Ku GY, et al. Genetic predictors of response to systemic therapy in Esophagogastric Cancer. Cancer Discov. 2018;8:49–58.PubMedCrossRef Janjigian YY, Sanchez-Vega F, Jonsson P, Chatila WK, Hechtman JF, Ku GY, et al. Genetic predictors of response to systemic therapy in Esophagogastric Cancer. Cancer Discov. 2018;8:49–58.PubMedCrossRef
26.
go back to reference Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.PubMedPubMedCentralCrossRef Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.PubMedPubMedCentralCrossRef
27.
go back to reference Li X, Shao C, Shi Y, Han W. Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. J Hematol Oncol. 2018;11:31.PubMedCrossRef Li X, Shao C, Shi Y, Han W. Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. J Hematol Oncol. 2018;11:31.PubMedCrossRef
28.
go back to reference Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. N Engl J Med. 2016;375:1823–33.PubMedCrossRef Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. N Engl J Med. 2016;375:1823–33.PubMedCrossRef
29.
go back to reference Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017;129:3419–27.PubMedPubMedCentralCrossRef Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017;129:3419–27.PubMedPubMedCentralCrossRef
30.
go back to reference Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:1483–92.PubMedCrossRef Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:1483–92.PubMedCrossRef
31.
go back to reference Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17:1590–8.PubMedPubMedCentralCrossRef Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17:1590–8.PubMedPubMedCentralCrossRef
33.
go back to reference Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung Cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12:208–22.PubMedCrossRef Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung Cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12:208–22.PubMedCrossRef
35.
go back to reference Li D, Chen R, Wang YW, Fornace AJ Jr, Li HH. Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells. Int J Radiat Biol. 2017;94:488–94.PubMedCrossRef Li D, Chen R, Wang YW, Fornace AJ Jr, Li HH. Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells. Int J Radiat Biol. 2017;94:488–94.PubMedCrossRef
36.
go back to reference Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, Guminski A, et al. Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in melanoma. Clin Cancer Res. 2017;23:5024–33.PubMedCrossRef Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, Guminski A, et al. Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in melanoma. Clin Cancer Res. 2017;23:5024–33.PubMedCrossRef
37.
go back to reference Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301.PubMedCrossRef Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301.PubMedCrossRef
38.
go back to reference Bocca P, Di Carlo E, Caruana I, Emionite L, Cilli M, De Angelis B, et al. Bevacizumab-mediated tumor vasculature remodelling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model. Oncoimmunology. 2017;7:e1378843.PubMedCrossRefPubMedCentral Bocca P, Di Carlo E, Caruana I, Emionite L, Cilli M, De Angelis B, et al. Bevacizumab-mediated tumor vasculature remodelling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model. Oncoimmunology. 2017;7:e1378843.PubMedCrossRefPubMedCentral
39.
go back to reference McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749–57.PubMedCrossRef McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749–57.PubMedCrossRef
43.
go back to reference Xing X, Guo J, Wen X, Ding G, Li B, Dong B, et al. Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients. Oncoimmunology. 2018;7:e1356144.PubMedCrossRef Xing X, Guo J, Wen X, Ding G, Li B, Dong B, et al. Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients. Oncoimmunology. 2018;7:e1356144.PubMedCrossRef
45.
go back to reference Tomioka N, Azuma M, Ikarashi M, Yamamoto M, Sato M, Watanabe KI, et al. The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC). Breast Cancer. 2018;25:34–42.PubMedCrossRef Tomioka N, Azuma M, Ikarashi M, Yamamoto M, Sato M, Watanabe KI, et al. The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC). Breast Cancer. 2018;25:34–42.PubMedCrossRef
48.
go back to reference Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for Cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22:1865–74.PubMedCrossRef Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for Cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22:1865–74.PubMedCrossRef
49.
go back to reference Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.PubMedPubMedCentralCrossRef Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.PubMedPubMedCentralCrossRef
50.
go back to reference Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, et al. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat Commun. 2018;9:741.PubMedPubMedCentralCrossRef Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, et al. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat Commun. 2018;9:741.PubMedPubMedCentralCrossRef
51.
go back to reference Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018;11:39.PubMedPubMedCentralCrossRef Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018;11:39.PubMedPubMedCentralCrossRef
53.
go back to reference Tremblay-LeMay R, Rastgoo N, Chang H. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway. J Hematol Oncol. 2018;11:46.PubMedPubMedCentralCrossRef Tremblay-LeMay R, Rastgoo N, Chang H. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway. J Hematol Oncol. 2018;11:46.PubMedPubMedCentralCrossRef
54.
go back to reference Teng F, Meng X, Kong L, Yu J. Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: a systematic review. Cancer Lett. 2018;414:166–73.PubMedCrossRef Teng F, Meng X, Kong L, Yu J. Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: a systematic review. Cancer Lett. 2018;414:166–73.PubMedCrossRef
55.
go back to reference Karachaliou N, Gonzalez-Cao M, Crespo G, Drozdowskyj A, Aldeguer E, Gimenez-Capitan A, et al. Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients. Ther Adv Med Oncol. 2018;10 1758834017749748 Karachaliou N, Gonzalez-Cao M, Crespo G, Drozdowskyj A, Aldeguer E, Gimenez-Capitan A, et al. Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients. Ther Adv Med Oncol. 2018;10 1758834017749748
56.
57.
go back to reference Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M, et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature. 2012;490:412–6.PubMedCrossRef Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M, et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature. 2012;490:412–6.PubMedCrossRef
58.
go back to reference Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009;69:2887–95.PubMedPubMedCentralCrossRef Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009;69:2887–95.PubMedPubMedCentralCrossRef
59.
go back to reference Baas M, Besancon A, Goncalves T, Valette F, Yagita H, Sawitzki B, et al. TGFbeta-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance. elife. 2016;5:e08133.PubMedPubMedCentralCrossRef Baas M, Besancon A, Goncalves T, Valette F, Yagita H, Sawitzki B, et al. TGFbeta-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance. elife. 2016;5:e08133.PubMedPubMedCentralCrossRef
60.
go back to reference Hodges TR, Ott M, Xiu J, Gatalica Z, Swensen J, Zhou S, et al. Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy. Neuro-Oncology. 2017;19:1047–57.PubMedPubMedCentralCrossRef Hodges TR, Ott M, Xiu J, Gatalica Z, Swensen J, Zhou S, et al. Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy. Neuro-Oncology. 2017;19:1047–57.PubMedPubMedCentralCrossRef
61.
go back to reference Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung Cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018;36:633–41.PubMedPubMedCentralCrossRef Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung Cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018;36:633–41.PubMedPubMedCentralCrossRef
62.
go back to reference Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16:2598–608.PubMedCrossRef Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16:2598–608.PubMedCrossRef
63.
go back to reference Yuza K, Nagahashi M, Watanabe S, Takabe K, Wakai T. Hypermutation and microsatellite instability in gastrointestinal cancers. Oncotarget. 2017;8:112103–15.PubMedPubMedCentralCrossRef Yuza K, Nagahashi M, Watanabe S, Takabe K, Wakai T. Hypermutation and microsatellite instability in gastrointestinal cancers. Oncotarget. 2017;8:112103–15.PubMedPubMedCentralCrossRef
64.
go back to reference Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377:2500–1.PubMedCrossRef Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377:2500–1.PubMedCrossRef
65.
go back to reference McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351:1463–9.PubMedPubMedCentralCrossRef McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351:1463–9.PubMedPubMedCentralCrossRef
67.
go back to reference Kim ST, Klempner SJ, Park SH, Park JO, Park YS, Lim HY, et al. Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy. Oncotarget. 2017;8:77415–23.PubMedPubMedCentral Kim ST, Klempner SJ, Park SH, Park JO, Park YS, Lim HY, et al. Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy. Oncotarget. 2017;8:77415–23.PubMedPubMedCentral
68.
go back to reference Yamashita H, Nakayama K, Ishikawa M, Nakamura K, Ishibashi T, Sanuki K, et al. Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer. Oncotarget. 2018;9:5652–64.PubMed Yamashita H, Nakayama K, Ishikawa M, Nakamura K, Ishibashi T, Sanuki K, et al. Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer. Oncotarget. 2018;9:5652–64.PubMed
69.
go back to reference Geiersbach KB, Samowitz WS. Microsatellite instability and colorectal cancer. Arch Pathol Lab Med. 2011;135:1269–77.PubMedCrossRef Geiersbach KB, Samowitz WS. Microsatellite instability and colorectal cancer. Arch Pathol Lab Med. 2011;135:1269–77.PubMedCrossRef
70.
go back to reference Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, Emami MH. Clinical aspects of microsatellite instability testing in colorectal Cancer. Adv Biomed Res. 2018;7:28.PubMedPubMedCentralCrossRef Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, Emami MH. Clinical aspects of microsatellite instability testing in colorectal Cancer. Adv Biomed Res. 2018;7:28.PubMedPubMedCentralCrossRef
71.
go back to reference Xiao X, Dong D, He W, Song L, Wang Q, Yue J, et al. Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer. Gynecol Oncol. 2018;149:146–54.PubMedCrossRef Xiao X, Dong D, He W, Song L, Wang Q, Yue J, et al. Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer. Gynecol Oncol. 2018;149:146–54.PubMedCrossRef
72.
go back to reference Jin Z, Yoon HH. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1. J Gastrointest Oncol. 2016;7:771–88.PubMedPubMedCentralCrossRef Jin Z, Yoon HH. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1. J Gastrointest Oncol. 2016;7:771–88.PubMedPubMedCentralCrossRef
73.
go back to reference Kumar R, Yu F, Zhen YH, Li B, Wang J, Yang Y, et al. PD-1 blockade restores impaired function of ex vivo expanded CD8(+) T cells and enhances apoptosis in mismatch repair deficient EpCAM(+)PD-L1(+) cancer cells. Onco Targets Ther. 2017;10:3453–65.PubMedPubMedCentralCrossRef Kumar R, Yu F, Zhen YH, Li B, Wang J, Yang Y, et al. PD-1 blockade restores impaired function of ex vivo expanded CD8(+) T cells and enhances apoptosis in mismatch repair deficient EpCAM(+)PD-L1(+) cancer cells. Onco Targets Ther. 2017;10:3453–65.PubMedPubMedCentralCrossRef
74.
go back to reference Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.PubMedPubMedCentralCrossRef Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.PubMedPubMedCentralCrossRef
75.
go back to reference Mills AM, Dill EA, Moskaluk CA, Dziegielewski J, Bullock TN, Dillon PM. The relationship between mismatch repair deficiency and PD-L1 expression in breast carcinoma. Am J Surg Pathol. 2018;42:183–91.PubMedCrossRef Mills AM, Dill EA, Moskaluk CA, Dziegielewski J, Bullock TN, Dillon PM. The relationship between mismatch repair deficiency and PD-L1 expression in breast carcinoma. Am J Surg Pathol. 2018;42:183–91.PubMedCrossRef
76.
go back to reference El Jabbour T, Ross JS, Sheehan CE, Affolter KE, Geiersbach KB, Boguniewicz A, et al. PD-L1 protein expression in tumour cells and immune cells in mismatch repair protein-deficient and -proficient colorectal cancer: the foundation study using the SP142 antibody and whole section immunohistochemistry. J Clin Pathol. 2018;71:46–51.PubMedCrossRef El Jabbour T, Ross JS, Sheehan CE, Affolter KE, Geiersbach KB, Boguniewicz A, et al. PD-L1 protein expression in tumour cells and immune cells in mismatch repair protein-deficient and -proficient colorectal cancer: the foundation study using the SP142 antibody and whole section immunohistochemistry. J Clin Pathol. 2018;71:46–51.PubMedCrossRef
77.
go back to reference Jiang L, Su X, Zhang T, Yin X, Zhang M, Fu H, et al. PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC). Oncotarget. 2017;8:26845–57.PubMedPubMedCentral Jiang L, Su X, Zhang T, Yin X, Zhang M, Fu H, et al. PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC). Oncotarget. 2017;8:26845–57.PubMedPubMedCentral
78.
go back to reference Li X, Lian Z, Wang S, Xing L, Yu J. Interactions between EGFR and PD-1/PD-L1 pathway: implications for treatment of NSCLC. Cancer Lett. 2018;418:1–9.PubMedCrossRef Li X, Lian Z, Wang S, Xing L, Yu J. Interactions between EGFR and PD-1/PD-L1 pathway: implications for treatment of NSCLC. Cancer Lett. 2018;418:1–9.PubMedCrossRef
79.
go back to reference Petrelli F, Maltese M, Tomasello G, Conti B, Borgonovo K, Cabiddu M, et al. Clinical and molecular predictors of PD-L1 expression in non-small-cell lung Cancer: systematic review and meta-analysis. Clin Lung Cancer. 2018;19:315–22.PubMedCrossRef Petrelli F, Maltese M, Tomasello G, Conti B, Borgonovo K, Cabiddu M, et al. Clinical and molecular predictors of PD-L1 expression in non-small-cell lung Cancer: systematic review and meta-analysis. Clin Lung Cancer. 2018;19:315–22.PubMedCrossRef
80.
go back to reference Lan B, Ma C, Zhang C, Chai S, Wang P, Ding L, et al. Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis. Oncotarget. 2018;9:7684–99.PubMedPubMedCentral Lan B, Ma C, Zhang C, Chai S, Wang P, Ding L, et al. Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis. Oncotarget. 2018;9:7684–99.PubMedPubMedCentral
81.
go back to reference Coelho MA, de Carne TS, Rana S, Zecchin D, Moore C, Molina-Arcas M, et al. Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. Immunity. 2017;47:1083–99. e6PubMedPubMedCentralCrossRef Coelho MA, de Carne TS, Rana S, Zecchin D, Moore C, Molina-Arcas M, et al. Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. Immunity. 2017;47:1083–99. e6PubMedPubMedCentralCrossRef
82.
go back to reference Cha YJ, Shim HS. PD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors. Oncotarget. 2017;8:89465–74.PubMedPubMedCentralCrossRef Cha YJ, Shim HS. PD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors. Oncotarget. 2017;8:89465–74.PubMedPubMedCentralCrossRef
83.
go back to reference Boichard A, Tsigelny IF, Kurzrock R. High expression of PD-1 ligands is associated with kataegis mutational signature and APOBEC3 alterations. Oncoimmunology. 2017;6:e1284719.PubMedPubMedCentralCrossRef Boichard A, Tsigelny IF, Kurzrock R. High expression of PD-1 ligands is associated with kataegis mutational signature and APOBEC3 alterations. Oncoimmunology. 2017;6:e1284719.PubMedPubMedCentralCrossRef
84.
go back to reference Gadducci A, Guerrieri ME. Immune checkpoint inhibitors in gynecological cancers: update of literature and perspectives of clinical research. Anticancer Res. 2017;37:5955–65.PubMed Gadducci A, Guerrieri ME. Immune checkpoint inhibitors in gynecological cancers: update of literature and perspectives of clinical research. Anticancer Res. 2017;37:5955–65.PubMed
85.
go back to reference Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung Cancer: a review. JAMA Oncol. 2016;2:1217–22.PubMedCrossRef Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung Cancer: a review. JAMA Oncol. 2016;2:1217–22.PubMedCrossRef
86.
87.
go back to reference Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9.PubMedPubMedCentralCrossRef Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9.PubMedPubMedCentralCrossRef
88.
go back to reference Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.PubMedCrossRef Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.PubMedCrossRef
89.
go back to reference Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7.PubMedCrossRef Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7.PubMedCrossRef
90.
go back to reference Daillere R, Vetizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45:931–43.PubMedCrossRef Daillere R, Vetizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45:931–43.PubMedCrossRef
91.
go back to reference Blacher E, Levy M, Tatirovsky E, Elinav E. Microbiome-modulated metabolites at the Interface of host immunity. J Immunol. 2017;198:572–80.PubMedCrossRef Blacher E, Levy M, Tatirovsky E, Elinav E. Microbiome-modulated metabolites at the Interface of host immunity. J Immunol. 2017;198:572–80.PubMedCrossRef
92.
go back to reference Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.PubMedPubMedCentralCrossRef Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.PubMedPubMedCentralCrossRef
94.
go back to reference Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann FJ, Weber LM, et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med. 2018;24:144–53.PubMedCrossRef Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann FJ, Weber LM, et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med. 2018;24:144–53.PubMedCrossRef
95.
go back to reference Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A. 2017;114:4993–8.PubMedPubMedCentralCrossRef Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A. 2017;114:4993–8.PubMedPubMedCentralCrossRef
96.
go back to reference Fujisawa Y, Yoshino K, Otsuka A, Funakoshi T, Fujimura T, Yamamoto Y, et al. Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population. Br J Dermatol. 2018; https://doi.org/10.1111/bjd.16427. Fujisawa Y, Yoshino K, Otsuka A, Funakoshi T, Fujimura T, Yamamoto Y, et al. Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population. Br J Dermatol. 2018; https://​doi.​org/​10.​1111/​bjd.​16427.
97.
go back to reference Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with Pembrolizumab. Clin Cancer Res. 2016;22:5487–96.PubMedPubMedCentralCrossRef Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with Pembrolizumab. Clin Cancer Res. 2016;22:5487–96.PubMedPubMedCentralCrossRef
98.
go back to reference Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann Oncol. 2017;28:1996–2001.PubMedCrossRef Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann Oncol. 2017;28:1996–2001.PubMedCrossRef
99.
go back to reference Iijima Y, Hirotsu Y, Amemiya K, Higashi S, Miyashita Y, Omata M. Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days. Respir Med Case Rep. 2017;22:31–3.PubMedPubMedCentral Iijima Y, Hirotsu Y, Amemiya K, Higashi S, Miyashita Y, Omata M. Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days. Respir Med Case Rep. 2017;22:31–3.PubMedPubMedCentral
100.
go back to reference Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, et al. Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunother Cancer. 2014;2:42.PubMedPubMedCentralCrossRef Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, et al. Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunother Cancer. 2014;2:42.PubMedPubMedCentralCrossRef
101.
go back to reference Yue C, Jiang Y, Li P, Wang Y, Xue J, Li N, et al. Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy. OncoImmunology. 2018; e1438111 Yue C, Jiang Y, Li P, Wang Y, Xue J, Li N, et al. Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy. OncoImmunology. 2018; e1438111
102.
go back to reference Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017;5:480–92.PubMedPubMedCentralCrossRef Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017;5:480–92.PubMedPubMedCentralCrossRef
103.
go back to reference Kruger S, Legenstein ML, Rosgen V, Haas M, Modest DP, Westphalen CB, et al. Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer. Oncoimmunology. 2017;6:e1310358.PubMedPubMedCentralCrossRef Kruger S, Legenstein ML, Rosgen V, Haas M, Modest DP, Westphalen CB, et al. Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer. Oncoimmunology. 2017;6:e1310358.PubMedPubMedCentralCrossRef
104.
go back to reference Nagato T, Ohkuri T, Ohara K, Hirata Y, Kishibe K, Komabayashi Y, et al. Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunol Immunother. 2017;66:877–90.PubMedCrossRef Nagato T, Ohkuri T, Ohara K, Hirata Y, Kishibe K, Komabayashi Y, et al. Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunol Immunother. 2017;66:877–90.PubMedCrossRef
105.
go back to reference Caponnetto S, Iannantuono GM, Barchiesi G, Magri V, Gelibter A, Cortesi E. Prolactin as a potential early predictive factor in metastatic non-small cell lung Cancer patients treated with Nivolumab. Oncology. 2017;93:62–6.PubMedCrossRef Caponnetto S, Iannantuono GM, Barchiesi G, Magri V, Gelibter A, Cortesi E. Prolactin as a potential early predictive factor in metastatic non-small cell lung Cancer patients treated with Nivolumab. Oncology. 2017;93:62–6.PubMedCrossRef
106.
go back to reference Yamazaki N, Kiyohara Y, Uhara H, Iizuka H, Uehara J, Otsuka F, et al. Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma. Cancer Sci. 2017;108:1022–31.PubMedPubMedCentralCrossRef Yamazaki N, Kiyohara Y, Uhara H, Iizuka H, Uehara J, Otsuka F, et al. Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma. Cancer Sci. 2017;108:1022–31.PubMedPubMedCentralCrossRef
107.
go back to reference Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016;7:12624.PubMedPubMedCentralCrossRef Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016;7:12624.PubMedPubMedCentralCrossRef
108.
go back to reference Dirkx AE, Oude Egbrink MG, Castermans K, van der Schaft DW, Thijssen VL, Dings RP, et al. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J. 2006;20:621–30.PubMedCrossRef Dirkx AE, Oude Egbrink MG, Castermans K, van der Schaft DW, Thijssen VL, Dings RP, et al. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J. 2006;20:621–30.PubMedCrossRef
109.
go back to reference Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018;19:405–15.PubMedCrossRef Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018;19:405–15.PubMedCrossRef
110.
go back to reference McKendry RT, Spalluto CM, Burke H, Nicholas B, Cellura D, Al-Shamkhani A, et al. Dysregulation of antiviral function of CD8(+) T cells in the chronic obstructive pulmonary disease lung. Role of the PD-1-PD-L1 Axis. Am J Respir Crit Care Med. 2016;193:642–51.PubMedPubMedCentralCrossRef McKendry RT, Spalluto CM, Burke H, Nicholas B, Cellura D, Al-Shamkhani A, et al. Dysregulation of antiviral function of CD8(+) T cells in the chronic obstructive pulmonary disease lung. Role of the PD-1-PD-L1 Axis. Am J Respir Crit Care Med. 2016;193:642–51.PubMedPubMedCentralCrossRef
111.
113.
go back to reference Faruki H, Mayhew GM, Serody JS, Hayes DN, Perou CM, Lai-Goldman M. Lung adenocarcinoma and squamous cell carcinoma gene expression subtypes demonstrate significant differences in tumor immune landscape. J Thorac Oncol. 2017;12:943–53.PubMedCrossRef Faruki H, Mayhew GM, Serody JS, Hayes DN, Perou CM, Lai-Goldman M. Lung adenocarcinoma and squamous cell carcinoma gene expression subtypes demonstrate significant differences in tumor immune landscape. J Thorac Oncol. 2017;12:943–53.PubMedCrossRef
114.
go back to reference Cortellini A, Bersanelli M, Buti S, Gambale E, Atzori F, Zoratto F, et al. Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study. Immunotherapy. 2018;10:643–55.PubMedCrossRef Cortellini A, Bersanelli M, Buti S, Gambale E, Atzori F, Zoratto F, et al. Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study. Immunotherapy. 2018;10:643–55.PubMedCrossRef
115.
go back to reference Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48:434–52.PubMedCrossRef Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48:434–52.PubMedCrossRef
116.
go back to reference Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, et al. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017;79:651–60.PubMedPubMedCentralCrossRef Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, et al. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017;79:651–60.PubMedPubMedCentralCrossRef
117.
go back to reference Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, et al. Pembrolizumab for platinum- and Cetuximab-refractory head and neck Cancer: results from a single-arm. Phase II Study J Clin Oncol. 2017;35:1542–9.PubMedCrossRef Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, et al. Pembrolizumab for platinum- and Cetuximab-refractory head and neck Cancer: results from a single-arm. Phase II Study J Clin Oncol. 2017;35:1542–9.PubMedCrossRef
118.
go back to reference Hui R, Garon EB, Goldman JW, Leighl NB, Hellmann MD, Patnaik A, et al. Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial. Ann Oncol. 2017;28:874–81.PubMedCrossRef Hui R, Garon EB, Goldman JW, Leighl NB, Hellmann MD, Patnaik A, et al. Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial. Ann Oncol. 2017;28:874–81.PubMedCrossRef
119.
go back to reference Daud AI, Wolchok JD, Robert C, Hwu WJ, Weber JS, Ribas A, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody Pembrolizumab in melanoma. J Clin Oncol. 2016;34:4102–9.PubMedPubMedCentralCrossRef Daud AI, Wolchok JD, Robert C, Hwu WJ, Weber JS, Ribas A, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody Pembrolizumab in melanoma. J Clin Oncol. 2016;34:4102–9.PubMedPubMedCentralCrossRef
120.
go back to reference Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung Cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35:3924–33.PubMedPubMedCentralCrossRef Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung Cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35:3924–33.PubMedPubMedCentralCrossRef
121.
go back to reference Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18:312–22.PubMedCrossRef Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18:312–22.PubMedCrossRef
122.
go back to reference Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.PubMedPubMedCentralCrossRef Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.PubMedPubMedCentralCrossRef
123.
go back to reference Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16:257–65.PubMedPubMedCentralCrossRef Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16:257–65.PubMedPubMedCentralCrossRef
124.
go back to reference Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33:1430–7.PubMedCrossRef Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33:1430–7.PubMedCrossRef
125.
go back to reference Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.PubMedCrossRef Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.PubMedCrossRef
126.
go back to reference Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.PubMedPubMedCentralCrossRef Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.PubMedPubMedCentralCrossRef
127.
go back to reference Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255–65.PubMedCrossRef Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255–65.PubMedCrossRef
128.
go back to reference Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.PubMedCrossRef Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.PubMedCrossRef
129.
go back to reference McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol. 2016;34:833–42.PubMedCrossRef McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol. 2016;34:833–42.PubMedCrossRef
130.
go back to reference Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.PubMedPubMedCentralCrossRef Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.PubMedPubMedCentralCrossRef
131.
go back to reference Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–46.PubMedCrossRef Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–46.PubMedCrossRef
132.
go back to reference Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, et al. Efficacy and safety of Durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol. 2017;3:e172411.PubMedPubMedCentralCrossRef Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, et al. Efficacy and safety of Durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol. 2017;3:e172411.PubMedPubMedCentralCrossRef
133.
go back to reference Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter. Phase Ib Study J Clin Oncol. 2017;35:2117–24.PubMedCrossRef Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter. Phase Ib Study J Clin Oncol. 2017;35:2117–24.PubMedCrossRef
134.
go back to reference Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–8.PubMedCrossRef Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–8.PubMedCrossRef
Metadata
Title
Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors
Authors
Ming Yi
Dechao Jiao
Hanxiao Xu
Qian Liu
Weiheng Zhao
Xinwei Han
Kongming Wu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0864-3

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