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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Review

Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance

Authors: Xingxiang Pu, Lin Wu, Dan Su, Weimin Mao, Bingliang Fang

Published in: BMC Cancer | Issue 1/2018

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Abstract

Recent breakthroughs in targeted therapy and immunotherapy have revolutionized the treatment of lung cancer, the leading cause of cancer-related deaths in the United States and worldwide. Here we provide an overview of recent progress in immune checkpoint blockade therapy for treatment of non-small cell lung cancer (NSCLC), and discuss biomarkers associated with the treatment responses, mechanisms underlying resistance and strategies to overcome resistance. The success of immune checkpoint blockade therapies is driven by immunogenicity of tumor cells, which is associated with mutation burden and neoantigen burden in cancers. Lymphocyte infiltration in cancer tissues and interferon-γ–induced PD-L1 expression in tumor microenvironments may serve as surrogate biomarkers for adaptive immune resistance and likelihood of responses to immune checkpoint blockade therapy. In contrast, weak immunogenicity of, and/or impaired antigen presentation in, tumor cells are primary causes of resistance to these therapies. Thus, approaches that increase immunogenicity of cancer cells and/or enhance immune cell recruitment to cancer sites will likely overcome resistance to immunotherapy.
Literature
1.
2.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef
3.
go back to reference Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med. 2015;373(17):1627–39.PubMedPubMedCentralCrossRef Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med. 2015;373(17):1627–39.PubMedPubMedCentralCrossRef
4.
go back to reference Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung Cancer. N Engl J Med. 2015;373(2):123–35.PubMedPubMedCentralCrossRef Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung Cancer. N Engl J Med. 2015;373(2):123–35.PubMedPubMedCentralCrossRef
5.
go back to reference Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed
6.
go back to reference Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–83.PubMedPubMedCentralCrossRef Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–83.PubMedPubMedCentralCrossRef
7.
go back to reference Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, 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(10066):255–65.CrossRefPubMed Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, 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(10066):255–65.CrossRefPubMed
8.
go back to reference Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, et al. Durvalumab after Chemoradiotherapy in stage III non-small-cell lung Cancer. N Engl J Med. 2017;377(20):1919–29.PubMedCrossRef Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, et al. Durvalumab after Chemoradiotherapy in stage III non-small-cell lung Cancer. N Engl J Med. 2017;377(20):1919–29.PubMedCrossRef
9.
go back to reference Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, et al. Overall survival with Durvalumab after Chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018. https://doi.org/10.1056/NEJMoa1809697 [Epub ahead of print]. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, et al. Overall survival with Durvalumab after Chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018. https://​doi.​org/​10.​1056/​NEJMoa1809697 [Epub ahead of print].
10.
go back to reference Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, Keegan P, Pazdur R. FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung Cancer with progression on or after platinum-based chemotherapy. Oncologist. 2016;21(5):634–42.PubMedPubMedCentralCrossRef Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, Keegan P, Pazdur R. FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung Cancer with progression on or after platinum-based chemotherapy. Oncologist. 2016;21(5):634–42.PubMedPubMedCentralCrossRef
11.
go back to reference Weinstock C, Khozin S, Suzman D, Zhang L, Tang S, Wahby S, Goldberg KB, Kim G, Pazdur R. U.S. Food and Drug Administration approval summary: Atezolizumab for metastatic non-small cell lung Cancer. Clin Cancer Res. 2017;23(16):4534–9.PubMedCrossRef Weinstock C, Khozin S, Suzman D, Zhang L, Tang S, Wahby S, Goldberg KB, Kim G, Pazdur R. U.S. Food and Drug Administration approval summary: Atezolizumab for metastatic non-small cell lung Cancer. Clin Cancer Res. 2017;23(16):4534–9.PubMedCrossRef
12.
go back to reference Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA approval summary: Pembrolizumab for the treatment of patients with metastatic non-small cell lung Cancer whose tumors express programmed death-ligand 1. Oncologist. 2016;21(5):643–50.PubMedPubMedCentralCrossRef Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA approval summary: Pembrolizumab for the treatment of patients with metastatic non-small cell lung Cancer whose tumors express programmed death-ligand 1. Oncologist. 2016;21(5):643–50.PubMedPubMedCentralCrossRef
14.
go back to reference Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D’Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, et al. Non-small cell lung Cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15(4):504–35.CrossRef Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D’Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, et al. Non-small cell lung Cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15(4):504–35.CrossRef
15.
go back to reference Gulley JL, Rajan A, Spigel DR, Iannotti N, Chandler J, Wong DJL, Leach J, Edenfield WJ, Wang D, Grote HJ, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN solid tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):599–610.PubMedPubMedCentralCrossRef Gulley JL, Rajan A, Spigel DR, Iannotti N, Chandler J, Wong DJL, Leach J, Edenfield WJ, Wang D, Grote HJ, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN solid tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):599–610.PubMedPubMedCentralCrossRef
16.
go back to reference Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.PubMedPubMedCentralCrossRef Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.PubMedPubMedCentralCrossRef
17.
go back to reference Davies AM, Rispens T, Ooijevaar-de Heer P, Gould HJ, Jefferis R, Aalberse RC, Sutton BJ. Structural determinants of unique properties of human IgG4-fc. J Mol Biol. 2014;426(3):630–44.PubMedPubMedCentralCrossRef Davies AM, Rispens T, Ooijevaar-de Heer P, Gould HJ, Jefferis R, Aalberse RC, Sutton BJ. Structural determinants of unique properties of human IgG4-fc. J Mol Biol. 2014;426(3):630–44.PubMedPubMedCentralCrossRef
18.
go back to reference Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, et al. Overall survival and long-term safety of Nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung Cancer. J Clin Oncol. 2015;33(18):2004–12.PubMedPubMedCentralCrossRef Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, et al. Overall survival and long-term safety of Nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung Cancer. J Clin Oncol. 2015;33(18):2004–12.PubMedPubMedCentralCrossRef
19.
go back to reference Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.PubMedPubMedCentralCrossRef Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.PubMedPubMedCentralCrossRef
20.
go back to reference Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, 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(3):257–65.PubMedPubMedCentralCrossRef Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, 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(3):257–65.PubMedPubMedCentralCrossRef
21.
go back to reference Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.CrossRefPubMed Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.CrossRefPubMed
22.
go back to reference Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. N Engl J Med. 2016;375(19):1823–33.CrossRefPubMed Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. N Engl J Med. 2016;375(19):1823–33.CrossRefPubMed
23.
go back to reference Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, 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(10030):1837–46.CrossRefPubMed Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, 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(10030):1837–46.CrossRefPubMed
24.
go back to reference Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, Watkins A, Mullins S, Chodorge M, Andrews J, et al. Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3(9):1052–62.PubMedCrossRef Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, Watkins A, Mullins S, Chodorge M, Andrews J, et al. Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3(9):1052–62.PubMedCrossRef
25.
go back to reference Oganesyan V, Gao C, Shirinian L, Wu H, Dall’Acqua WF. Structural characterization of a human fc fragment engineered for lack of effector functions. Acta Crystallogr D Biol Crystallogr. 2008;64(Pt 6):700–4.PubMedPubMedCentralCrossRef Oganesyan V, Gao C, Shirinian L, Wu H, Dall’Acqua WF. Structural characterization of a human fc fragment engineered for lack of effector functions. Acta Crystallogr D Biol Crystallogr. 2008;64(Pt 6):700–4.PubMedPubMedCentralCrossRef
26.
go back to reference Powles T, O’Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, 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(9):e172411.PubMedPubMedCentralCrossRef Powles T, O’Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, 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(9):e172411.PubMedPubMedCentralCrossRef
27.
go back to reference Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, Corral Jaime J, Gray JE, Powderly J, Chouaid C, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19(4):521–36.PubMedCrossRefPubMedCentral Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, Corral Jaime J, Gray JE, Powderly J, Chouaid C, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19(4):521–36.PubMedCrossRefPubMedCentral
28.
go back to reference Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.PubMedPubMedCentralCrossRef Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.PubMedPubMedCentralCrossRef
29.
go back to reference Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–99.PubMedPubMedCentralCrossRef Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–99.PubMedPubMedCentralCrossRef
30.
go back to reference Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.PubMedPubMedCentralCrossRef Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.PubMedPubMedCentralCrossRef
31.
go back to reference Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.PubMedPubMedCentralCrossRef Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.PubMedPubMedCentralCrossRef
32.
go back to reference Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103.PubMedPubMedCentralCrossRef Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103.PubMedPubMedCentralCrossRef
33.
go back to reference Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-97.PubMedCrossRef Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-97.PubMedCrossRef
34.
go back to reference Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.PubMedPubMedCentralCrossRef Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.PubMedPubMedCentralCrossRef
35.
go back to reference Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.PubMedPubMedCentralCrossRef Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.PubMedPubMedCentralCrossRef
37.
go back to reference Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, et al. First-line Nivolumab in stage IV or recurrent non-small-cell lung Cancer. N Engl J Med. 2017;376(25):2415–26.CrossRefPubMedPubMedCentral Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, et al. First-line Nivolumab in stage IV or recurrent non-small-cell lung Cancer. N Engl J Med. 2017;376(25):2415–26.CrossRefPubMedPubMedCentral
38.
go back to reference Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, et al. Nivolumab plus Ipilimumab in lung Cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–104.CrossRefPubMedPubMedCentral Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, et al. Nivolumab plus Ipilimumab in lung Cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–104.CrossRefPubMedPubMedCentral
39.
go back to reference Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, Ni A, Novik JB, Mangarin LMB, Abu-Akeel M, et al. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell. 2018;33(5):843–852.e844.PubMedPubMedCentralCrossRef Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, Ni A, Novik JB, Mangarin LMB, Abu-Akeel M, et al. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell. 2018;33(5):843–852.e844.PubMedPubMedCentralCrossRef
41.
go back to reference Gottlieb NL. Pharmacology of auranofin: overview and update. Scand J Rheumatol Suppl. 1986;63:19–28.PubMed Gottlieb NL. Pharmacology of auranofin: overview and update. Scand J Rheumatol Suppl. 1986;63:19–28.PubMed
42.
go back to reference Campbell BB, Light N, Fabrizio D, Zatzman M, Fuligni F, de Borja R, Davidson S, Edwards M, Elvin JA, Hodel KP, et al. Comprehensive Analysis of Hypermutation in Human Cancer. Cell. 2017;171(5):1042–1056.e1010.PubMedPubMedCentralCrossRef Campbell BB, Light N, Fabrizio D, Zatzman M, Fuligni F, de Borja R, Davidson S, Edwards M, Elvin JA, Hodel KP, et al. Comprehensive Analysis of Hypermutation in Human Cancer. Cell. 2017;171(5):1042–1056.e1010.PubMedPubMedCentralCrossRef
43.
go back to reference Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993;75(6):1227–36.PubMedCrossRef Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993;75(6):1227–36.PubMedCrossRef
44.
go back to reference Bhattacharyya NP, Skandalis A, Ganesh A, Groden J, Meuth M. Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci U S A. 1994;91(14):6319–23.PubMedPubMedCentralCrossRef Bhattacharyya NP, Skandalis A, Ganesh A, Groden J, Meuth M. Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci U S A. 1994;91(14):6319–23.PubMedPubMedCentralCrossRef
45.
go back to reference Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.PubMedPubMedCentralCrossRef Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.PubMedPubMedCentralCrossRef
46.
go back to reference Shah SN, Hile SE, Eckert KA. Defective mismatch repair, microsatellite mutation bias, and variability in clinical cancer phenotypes. Cancer Res. 2010;70(2):431–5.PubMedPubMedCentralCrossRef Shah SN, Hile SE, Eckert KA. Defective mismatch repair, microsatellite mutation bias, and variability in clinical cancer phenotypes. Cancer Res. 2010;70(2):431–5.PubMedPubMedCentralCrossRef
47.
48.
go back to reference Simpson AJ, Caballero OL, Pena SD. Microsatellite instability as a tool for the classification of gastric cancer. Trends Mol Med. 2001;7(2):76–80.PubMedCrossRef Simpson AJ, Caballero OL, Pena SD. Microsatellite instability as a tool for the classification of gastric cancer. Trends Mol Med. 2001;7(2):76–80.PubMedCrossRef
49.
go back to reference Takamochi K, Takahashi F, Suehara Y, Sato E, Kohsaka S, Hayashi T, Kitano S, Uneno T, Kojima S, Takeuchi K, et al. DNA mismatch repair deficiency in surgically resected lung adenocarcinoma: microsatellite instability analysis using the Promega panel. Lung Cancer. 2017;110:26–31.PubMedCrossRef Takamochi K, Takahashi F, Suehara Y, Sato E, Kohsaka S, Hayashi T, Kitano S, Uneno T, Kojima S, Takeuchi K, et al. DNA mismatch repair deficiency in surgically resected lung adenocarcinoma: microsatellite instability analysis using the Promega panel. Lung Cancer. 2017;110:26–31.PubMedCrossRef
50.
go back to reference Warth A, Korner S, Penzel R, Muley T, Dienemann H, Schirmacher P, von Knebel-Doeberitz M, Weichert W, Kloor M. Microsatellite instability in pulmonary adenocarcinomas: a comprehensive study of 480 cases. Virchows Arch. 2016;468(3):313–9.PubMedCrossRef Warth A, Korner S, Penzel R, Muley T, Dienemann H, Schirmacher P, von Knebel-Doeberitz M, Weichert W, Kloor M. Microsatellite instability in pulmonary adenocarcinomas: a comprehensive study of 480 cases. Virchows Arch. 2016;468(3):313–9.PubMedCrossRef
51.
go back to reference Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.[Erratum appears in Nat Med 2002 Sep.8(9):1039]. Nat Med. 2002;8(8):793–800.CrossRefPubMed Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.[Erratum appears in Nat Med 2002 Sep.8(9):1039]. Nat Med. 2002;8(8):793–800.CrossRefPubMed
52.
go back to reference Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116.PubMedPubMedCentralCrossRef Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116.PubMedPubMedCentralCrossRef
53.
go back to reference Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung Cancer. Clin Cancer Res. 2017;23(2):370–8.PubMedCrossRef Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung Cancer. Clin Cancer Res. 2017;23(2):370–8.PubMedCrossRef
54.
go back to reference Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355–63.PubMedCrossRef Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355–63.PubMedCrossRef
55.
go back to reference Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, et al. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell. 2014;25(5):590–604.PubMedPubMedCentralCrossRef Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, et al. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell. 2014;25(5):590–604.PubMedPubMedCentralCrossRef
56.
go back to reference Muhlbauer M, Fleck M, Schutz C, Weiss T, Froh M, Blank C, Scholmerich J, Hellerbrand C. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol. 2006;45(4):520–8.PubMedCrossRef Muhlbauer M, Fleck M, Schutz C, Weiss T, Froh M, Blank C, Scholmerich J, Hellerbrand C. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol. 2006;45(4):520–8.PubMedCrossRef
57.
go back to reference Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006;580(3):755–62.PubMedCrossRef Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006;580(3):755–62.PubMedCrossRef
58.
go back to reference Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra137.CrossRef Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra137.CrossRef
62.
64.
go back to reference McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.PubMedPubMedCentralCrossRef McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.PubMedPubMedCentralCrossRef
65.
go back to reference Schvartsman G, Ferrarotto R, Massarelli E. Checkpoint inhibitors in lung cancer: latest developments and clinical potential. Ther Advn Med Oncol. 2016;8(6):460–73.CrossRef Schvartsman G, Ferrarotto R, Massarelli E. Checkpoint inhibitors in lung cancer: latest developments and clinical potential. Ther Advn Med Oncol. 2016;8(6):460–73.CrossRef
66.
go back to reference Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14(16):5220–7.PubMedCrossRef Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14(16):5220–7.PubMedCrossRef
67.
go back to reference Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, et al. Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113(6):1387–95.PubMedCrossRef Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, et al. Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113(6):1387–95.PubMedCrossRef
68.
go back to reference Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S, Pirker R, Douillard JY, Le Chevalier T, Filipits M, et al. Prognostic effect of tumor lymphocytic infiltration in Resectable non-small-cell lung Cancer. J Clin Oncol. 2016;34(11):1223–30.PubMedPubMedCentralCrossRef Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S, Pirker R, Douillard JY, Le Chevalier T, Filipits M, et al. Prognostic effect of tumor lymphocytic infiltration in Resectable non-small-cell lung Cancer. J Clin Oncol. 2016;34(11):1223–30.PubMedPubMedCentralCrossRef
69.
go back to reference Geng Y, Shao Y, He W, Hu W, Xu Y, Chen J, Wu C, Jiang J. Prognostic role of tumor-infiltrating lymphocytes in lung Cancer: a meta-analysis. Cell Physiol Biochem. 2015;37(4):1560–71.PubMedCrossRef Geng Y, Shao Y, He W, Hu W, Xu Y, Chen J, Wu C, Jiang J. Prognostic role of tumor-infiltrating lymphocytes in lung Cancer: a meta-analysis. Cell Physiol Biochem. 2015;37(4):1560–71.PubMedCrossRef
70.
go back to reference Djenidi F, Adam J, Goubar A, Durgeau A, Meurice G, de Montpreville V, Validire P, Besse B, Mami-Chouaib F. CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J Immunol. 2015;194(7):3475–86.PubMedCrossRef Djenidi F, Adam J, Goubar A, Durgeau A, Meurice G, de Montpreville V, Validire P, Besse B, Mami-Chouaib F. CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J Immunol. 2015;194(7):3475–86.PubMedCrossRef
71.
go back to reference Ganesan AP, Clarke J, Wood O, Garrido-Martin EM, Chee SJ, Mellows T, Samaniego-Castruita D, Singh D, Seumois G, Alzetani A, et al. Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nat Immunol. 2017;18(8):940–50.PubMedPubMedCentralCrossRef Ganesan AP, Clarke J, Wood O, Garrido-Martin EM, Chee SJ, Mellows T, Samaniego-Castruita D, Singh D, Seumois G, Alzetani A, et al. Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nat Immunol. 2017;18(8):940–50.PubMedPubMedCentralCrossRef
72.
go back to reference Koh J, Kim S, Kim MY, Go H, Jeon YK, Chung DH. Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma. Oncotarget. 2017;8(8):13762–9.PubMedPubMedCentralCrossRef Koh J, Kim S, Kim MY, Go H, Jeon YK, Chung DH. Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma. Oncotarget. 2017;8(8):13762–9.PubMedPubMedCentralCrossRef
73.
go back to reference Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang S, et al. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood. 2011;117(3):808–14.PubMedPubMedCentralCrossRef Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang S, et al. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood. 2011;117(3):808–14.PubMedPubMedCentralCrossRef
74.
go back to reference Hinrichs CS, Borman ZA, Cassard L, Gattinoni L, Spolski R, Yu Z, Sanchez-Perez L, Muranski P, Kern SJ, Logun C, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci U S A. 2009;106(41):17469–74.PubMedPubMedCentralCrossRef Hinrichs CS, Borman ZA, Cassard L, Gattinoni L, Spolski R, Yu Z, Sanchez-Perez L, Muranski P, Kern SJ, Logun C, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci U S A. 2009;106(41):17469–74.PubMedPubMedCentralCrossRef
75.
go back to reference Klebanoff CA, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones AR, Finkelstein SE, Palmer DC, Antony PA, Hwang ST, Rosenberg SA, et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A. 2005;102(27):9571–6.PubMedPubMedCentralCrossRef Klebanoff CA, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones AR, Finkelstein SE, Palmer DC, Antony PA, Hwang ST, Rosenberg SA, et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A. 2005;102(27):9571–6.PubMedPubMedCentralCrossRef
76.
go back to reference Inozume T, Hanada K, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA, Yang JC. Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother. 2010;33(9):956–64.PubMedPubMedCentralCrossRef Inozume T, Hanada K, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA, Yang JC. Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother. 2010;33(9):956–64.PubMedPubMedCentralCrossRef
77.
go back to reference Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, et al. PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Invest. 2014;124(5):2246–59.PubMedPubMedCentralCrossRef Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, et al. PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Invest. 2014;124(5):2246–59.PubMedPubMedCentralCrossRef
78.
go back to reference Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29–37.CrossRefPubMed Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29–37.CrossRefPubMed
79.
go back to reference Baitsch L, Legat A, Barba L, Fuertes Marraco SA, Rivals JP, Baumgaertner P, Christiansen-Jucht C, Bouzourene H, Rimoldi D, Pircher H, et al. Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One. 2012;7(2):e30852.PubMedPubMedCentralCrossRef Baitsch L, Legat A, Barba L, Fuertes Marraco SA, Rivals JP, Baumgaertner P, Christiansen-Jucht C, Bouzourene H, Rimoldi D, Pircher H, et al. Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One. 2012;7(2):e30852.PubMedPubMedCentralCrossRef
80.
go back to reference Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016;22(4):433–8.PubMedCrossRefPubMedCentral Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016;22(4):433–8.PubMedCrossRefPubMedCentral
81.
go back to reference Cohen CJ, Gartner JJ, Horovitz-Fried M, Shamalov K, Trebska-McGowan K, Bliskovsky VV, Parkhurst MR, Ankri C, Prickett TD, Crystal JS, et al. Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes. J Clin Invest. 2015;125(10):3981–91.PubMedPubMedCentralCrossRef Cohen CJ, Gartner JJ, Horovitz-Fried M, Shamalov K, Trebska-McGowan K, Bliskovsky VV, Parkhurst MR, Ankri C, Prickett TD, Crystal JS, et al. Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes. J Clin Invest. 2015;125(10):3981–91.PubMedPubMedCentralCrossRef
82.
go back to reference Stevanovic S, Pasetto A, Helman SR. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017;356(6334):200–5.PubMedCrossRefPubMedCentral Stevanovic S, Pasetto A, Helman SR. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017;356(6334):200–5.PubMedCrossRefPubMedCentral
83.
go back to reference Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–5.PubMedCrossRefPubMedCentral Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–5.PubMedCrossRefPubMedCentral
84.
go back to reference Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, et al. T-cell transfer therapy targeting mutant KRAS in Cancer. N Engl J Med. 2016;375(23):2255–62.PubMedPubMedCentralCrossRef Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, et al. T-cell transfer therapy targeting mutant KRAS in Cancer. N Engl J Med. 2016;375(23):2255–62.PubMedPubMedCentralCrossRef
85.
go back to reference Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8:822–35.PubMedCrossRefPubMedCentral Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8:822–35.PubMedCrossRefPubMedCentral
86.
go back to reference Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, Yang JC. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung Cancer-a meta-analysis. J Thorac Oncol. 2017;12(2):403–7.PubMedCrossRef Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, Yang JC. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung Cancer-a meta-analysis. J Thorac Oncol. 2017;12(2):403–7.PubMedCrossRef
87.
go back to reference Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23(15):4242–50.PubMedPubMedCentralCrossRef Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23(15):4242–50.PubMedPubMedCentralCrossRef
88.
go back to reference Fang B, Mehran RJ, Heymach JV, Swisher SG. Predictive biomarkers in precision medicine and drug development against lung cancer. Chin J Cancer. 2015;34(1):26.PubMedCentralCrossRef Fang B, Mehran RJ, Heymach JV, Swisher SG. Predictive biomarkers in precision medicine and drug development against lung cancer. Chin J Cancer. 2015;34(1):26.PubMedCentralCrossRef
89.
go back to reference Holmgaard RB, Holmgaard RB. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210(7):1389–402.PubMedPubMedCentralCrossRef Holmgaard RB, Holmgaard RB. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210(7):1389–402.PubMedPubMedCentralCrossRef
90.
go back to reference Braun D, Longman RS, Albert ML. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood. 2005;106(7):2375–81.PubMedPubMedCentralCrossRef Braun D, Longman RS, Albert ML. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood. 2005;106(7):2375–81.PubMedPubMedCentralCrossRef
91.
go back to reference Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009;113(24):6102–11.PubMedPubMedCentralCrossRef Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009;113(24):6102–11.PubMedPubMedCentralCrossRef
92.
go back to reference Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.PubMedPubMedCentralCrossRef Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.PubMedPubMedCentralCrossRef
93.
go back to reference Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman-Saint Victor C, Cucolo L, Lee DS, Pauken KE, Huang AC, et al. Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade. Cell. 2016;167(6):1540–1554.e1512.PubMedPubMedCentralCrossRef Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman-Saint Victor C, Cucolo L, Lee DS, Pauken KE, Huang AC, et al. Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade. Cell. 2016;167(6):1540–1554.e1512.PubMedPubMedCentralCrossRef
95.
go back to reference Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29.PubMedPubMedCentralCrossRef Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29.PubMedPubMedCentralCrossRef
96.
97.
go back to reference Masopust D, Schenkel JM. The integration of T cell migration, differentiation and function. Nat Rev Immunol. 2013;13(5):309–20.CrossRefPubMed Masopust D, Schenkel JM. The integration of T cell migration, differentiation and function. Nat Rev Immunol. 2013;13(5):309–20.CrossRefPubMed
99.
go back to reference Yan X, Wang L, Zhang R, Pu X, Wu S, Yu L, Meraz IM, Zhang X, Wang JF, Gibbons DL, et al. Overcoming resistance to anti-PD immunotherapy in a syngeneic mouse lung cancer model using locoregional virotherapy. Oncoimmunol. 2018;7(1):e1376156.CrossRef Yan X, Wang L, Zhang R, Pu X, Wu S, Yu L, Meraz IM, Zhang X, Wang JF, Gibbons DL, et al. Overcoming resistance to anti-PD immunotherapy in a syngeneic mouse lung cancer model using locoregional virotherapy. Oncoimmunol. 2018;7(1):e1376156.CrossRef
100.
go back to reference Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017;170(6):1109–1119.e1110.CrossRefPubMedPubMedCentral Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017;170(6):1109–1119.e1110.CrossRefPubMedPubMedCentral
101.
go back to reference Tang H, Wang Y, Chlewicki LK, Zhang Y, Guo J, Liang W, Wang J, Wang X, Fu YX. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 2016;29(3):285–96.PubMedPubMedCentralCrossRef Tang H, Wang Y, Chlewicki LK, Zhang Y, Guo J, Liang W, Wang J, Wang X, Fu YX. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 2016;29(3):285–96.PubMedPubMedCentralCrossRef
102.
go back to reference Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde N, Jansen P, Gaffal E, Steitz J, Tolba R, Kalinke U, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87.PubMedCrossRef Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde N, Jansen P, Gaffal E, Steitz J, Tolba R, Kalinke U, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87.PubMedCrossRef
103.
go back to reference Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–91.PubMedPubMedCentralCrossRef Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–91.PubMedPubMedCentralCrossRef
104.
go back to reference McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung Cancer. JAMA Oncol. 2016;2(1):46–54.PubMedPubMedCentralCrossRef McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung Cancer. JAMA Oncol. 2016;2(1):46–54.PubMedPubMedCentralCrossRef
105.
go back to reference Nakamura S, Hayashi K, Imaoka Y, Kitamura Y, Akazawa Y, Tabata K, Groen R, Tsuchiya T, Yamasaki N, Nagayasu T, et al. Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer. PLoS One. 2017;12(10):e0186192.PubMedPubMedCentralCrossRef Nakamura S, Hayashi K, Imaoka Y, Kitamura Y, Akazawa Y, Tabata K, Groen R, Tsuchiya T, Yamasaki N, Nagayasu T, et al. Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer. PLoS One. 2017;12(10):e0186192.PubMedPubMedCentralCrossRef
106.
go back to reference Pinato DJ, Shiner RJ, White SD, Black JR, Trivedi P, Stebbing J, Sharma R, Mauri FA. Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer: implications for immunotherapy. Oncoimmunol. 2016;5(9):e1213934.CrossRef Pinato DJ, Shiner RJ, White SD, Black JR, Trivedi P, Stebbing J, Sharma R, Mauri FA. Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer: implications for immunotherapy. Oncoimmunol. 2016;5(9):e1213934.CrossRef
107.
go back to reference Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A, Sica GL, Yu K, Koenig L, Patel NT, 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(19):4993–8.PubMedPubMedCentralCrossRef Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A, Sica GL, Yu K, Koenig L, Patel NT, 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(19):4993–8.PubMedPubMedCentralCrossRef
108.
go back to reference Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunol. 2014;3(9):e955691.CrossRef Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunol. 2014;3(9):e955691.CrossRef
109.
go back to reference Galluzzi L, Kepp O, Kroemer G. Immunogenic cell death in radiation therapy. Oncoimmunol. 2013;2(10):e26536.CrossRef Galluzzi L, Kepp O, Kroemer G. Immunogenic cell death in radiation therapy. Oncoimmunol. 2013;2(10):e26536.CrossRef
110.
go back to reference Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget. 2014;5(2):403–16.PubMedCrossRef Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget. 2014;5(2):403–16.PubMedCrossRef
111.
go back to reference Beyranvand Nejad E, van der Sluis TC, van Duikeren S, Yagita H, Janssen GM, van Veelen PA, Melief CJ, van der Burg SH, Arens R. Tumor eradication by cisplatin is sustained by CD80/86-mediated Costimulation of CD8+ T cells. Cancer Res. 2016;76(20):6017–29.PubMedCrossRef Beyranvand Nejad E, van der Sluis TC, van Duikeren S, Yagita H, Janssen GM, van Veelen PA, Melief CJ, van der Burg SH, Arens R. Tumor eradication by cisplatin is sustained by CD80/86-mediated Costimulation of CD8+ T cells. Cancer Res. 2016;76(20):6017–29.PubMedCrossRef
112.
go back to reference Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, Murata K, Fujii H, Nakano T, Kono K. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 2012;72(16):3967–76.PubMedCrossRef Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, Murata K, Fujii H, Nakano T, Kono K. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 2012;72(16):3967–76.PubMedCrossRef
113.
go back to reference Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung Cancer. N Engl J Med. 2018;378(22):2078–92.PubMedCrossRef Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung Cancer. N Engl J Med. 2018;378(22):2078–92.PubMedCrossRef
114.
Metadata
Title
Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance
Authors
Xingxiang Pu
Lin Wu
Dan Su
Weimin Mao
Bingliang Fang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4990-5

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