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Nature, 2014, 515(7528): 572-576. a phase II study( FIR)of MPDL3280A(anti-PDLI)in PD-Ll-selected 39 Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer patients with non-small cell lung cancer(NSCLC). J Clin Oncol, 2015, immunotherapy targets tumour-specific mutant antigens. Nature, 2014, 515(7528):577-581 5 Horn L, Spigel DR, Gettinger SN, et al. Clinical activity, safety and 40 Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of predictive biomarkers of the engineered antibody MPDL3280A (anti- oncogenic drivers in lung cancers to select targeted drugs. JAMA, 2014, PDLI)in non-small cell lung cancer(NSCLC): update from a phase Ia 311(19):198-2006 study. JClin Oncol, 2015, 33(suppl): abstr 8029 41 Akbay EA, Koyama S, Carretero J, et al. Activation of the PD-l pathway 6 Segal NH, Antonia S], Brahmer JR, et al. Preliminary data from a multi- contributes to immune escape in EGFR-driven lung tumors. Cancer arm expansion study of MEDI4736, an anti-PD-Ll antibody. J Clin Discov.2013,3(12):1355-1363 ncol,2014,32(suppl): abstr 3002. 42 Azuma K, Ota K, Kawahara A, et aL. Association of PD-Ll overexpression 27 Rizvi NA, Brahmer R, Ou SHI, et al. Safety and clinical activity of with activating EGFR mutations in surgically resected non small-cell MEDI4736, an anti-programmed cell death-ligand 1(PD-L1)antibody, lung cancer. Ann Oncol, 2014, 25(10):1935-1940. 29 G patients with non-small cell lung cancer(NSCLC). J Clin Oncol, 2015, 43 D'Incecco A, AndreozziM, LudoviniV,et al.PD-IandPD-LI expression 63(suPpl): abstr 80 in molecularly selected non-small-cell lung cancer patients. Br J Cancer, Gulley JL, Spigel D, Kelly K. Avelumab(MSB0010718C), an anti-PD-Li 2015,112(1):95-102. antibody, in advanced NSCLC patients: A phase Ib, open-label expansion 44 Tang Y, Fang W, Zhang Y, et al. The association between PD-LI and trial in patients progressing after platinum-based chemotherapy. J Clin EGFR status and the prognostic value of PD-Ll in advanced non-sm Oncol, 2015,33(suppl): abstr 8034 cell lung cancer patients treated with EGFR-TKIs. Oncotarget, 2015. ishi J, Yamazaki K, Azuma M, et al. B7-HI expression on non 6(16):14209-14219 small cell lung cancer cells and its relationship with tumor-infiltrating 45 Yang CY, Lin MW, Chang YL, et al. Programmed cell death-ligand lymphocytes and their PD-l expression. Clin Cancer Res, 2004, 10(15) expression in surgically resected stage I pulmonary adenocarcinoma and 5094-5100 its correlation with driver mutations and clinical outcomes. Eur J Cancer, 30 Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 14,50(7):1361-1369 expression in non-small cell lung cancer. Lab Invest, 2014, 94(1): 46 GainorJE, Sequist LV, Shaw AT, et al. Clinical correlation and frequency 07-116 of programmed death ligand-1(PD-LI)expression in EGFR-mutant and 31 Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation ALK-rearranged non-small cell lung cancer(NSCLC). J Clin Oncol, mmunotherapy-inhibiting programmed death-ligand I and programmed 2015, 33(suppl): abstr 8012 death-1. Clin Cancer Res, 2012, 18(24): 6580-6587 47 Chen N, Fang W, ZhanJ, et al. Up-regulation of PD-LI by egfr activation 32 Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces mediates the immune escape in EGFR-driven NSCLC: Implication responses by inhibiting adaptive immune resistance. Nature, 2014, for optional immune targeted therapy for NSCLC Patients with EGFR 515(7528):568-571 mutation. J Thorac Oncol, 2015, 10(6):910-923 33 Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab 48 Rizvi NA, Hellmann MD, Snyder A, et aL. Cancer immunology. n Advanced Melanoma. N EnglJ Med, 2015, 372(26): 2521-2532 Mutational landscape determines sensitivity to PD-I blockade in non 4 Keir ME, Butte MJ, Freeman G], et al. PD-l and its ligands in tolerance small cell lung cancer. Science, 2015, 348(6230): 124-128. and immunity. Annu Rev Immunol, 2008, 26:677-704 49 Huard B, Gaulard P, Faure F, et al. Cellular expression and tissue 35 Curran MA, Montalvo W, Yagita H, et al. PD-l and CTLA-4 combination distribution of the human LAG-3-encoded protein, an MHC class II blockade expands infiltrating T cells and reduces regulatory T and ligand Immunogenetics, 1994, 39(3): 213-217. myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA, 50 Triebel F, Jitsukawa S, Baixeras E, et aL. LAG-3, a novel lymphocyte 2010,107(9):4275-4280 activation gene closely related to CD4. J Exp Med, 1990, 171(5) 36 Hellmann MD, Creelan BC, Woo K, et al. Smoking history and sponse to nivolumab in patients with advanced NSCLCs [abstract]. 51 Kisielow M, Kisielow J, Capoferri-Sollami G, et al. Expression of 21994-2015ChinaAcademicJournalElectronicPublishingHouse.alLrightsreservedhttp://www.cnki.net·712· 中国肺癌杂志2 0 1 5年1 1月第1 8卷第1 1期 Chin J Lung Cancer, November 2015, Vol.18, No.11 22 Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528): 563-567. 23 Spira A, Park K, Mazières J, et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). J Clin Oncol, 2015, 33(suppl): abstr 8010. 24 Spigel DR, Chaft JE, Gettinger SN, et al. Clinical activity and safety from a phase II study (FIR) of MPDL3280A (anti-PDL1) in PD-L1–selected patients with non-small cell lung cancer (NSCLC). J Clin Oncol, 2015, 33(suppl): abstr 8028. 25 Horn L, Spigel DR, Gettinger SN, et al. Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti￾PDL1) in non-small cell lung cancer (NSCLC): update from a phase Ia study. J Clin Oncol, 2015, 33(suppl): abstr 8029. 26 Segal NH, Antonia SJ, Brahmer JR, et al. Preliminary data from a multi￾arm expansion study of MEDI4736, an anti-PD-L1 antibody. J Clin Oncol, 2014, 32(suppl): abstr 3002. 27 Rizvi NA, Brahmer R, Ou SHI, et al. Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). J Clin Oncol, 2015, 33(suppl): abstr 8032. 28 Gulley JL, Spigel D, Kelly K. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: A phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy. J Clin Oncol, 2015, 33(suppl): abstr 8034. 29 Konishi J, Yamazaki K, Azuma M, et al. B7-H1 expression on non￾small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res, 2004, 10(15): 5094-5100. 30 Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest, 2014, 94(1): 107-116. 31 Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res, 2012, 18(24): 6580-6587. 32 Tumeh PC, Har view CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 2014, 515(7528): 568-571. 33 Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med, 2015, 372(26): 2521-2532. 34 Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008, 26: 677-704. 35 Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A, 2010, 107(9): 4275-4280. 36 Hel l ma n n M D, Creela n BC , Woo K , et al. Smok i ng h istor y a nd response to nivolumab in patients with advanced NSCLCs [abstract]. In: Proceedings of the ESMO 2014 Congress; 2014 Sep 26-30; Madrid, Spain. Lugano (Switzerland): European Society for Medical Oncology; 2014. Abstract nr 1229PD. 37 Melero I, Lasarte JJ. Genetic basis for clinical response to CTLA-4 blockade. N Engl J Med, 2015, 372(8): 783. 38 Yadav M, Jhunjhunwala S, Phung QT, et al. Predicting immunogenic t u mou r mutat ions by combi n i ng mass spec t romet r y a nd exome sequencing. Nature, 2014, 515(7528): 572-576. 39 Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature, 2014, 515(7528): 577-581. 40 Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA, 2014, 311(19): 1998-2006. 41 Akbay EA, Koyama S, Carretero J, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov, 2013, 3(12): 1355-1363. 42 Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected non small-cell lung cancer. Ann Oncol, 2014, 25(10): 1935-1940. 43 D'Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer, 2015, 112(1): 95-102. 44 Tang Y, Fang W, Zhang Y, et al. The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs. Oncotarget, 2015, 6(16): 14209-14219. 45 Yang CY, Lin MW, Chang YL, et al. Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer, 2014, 50(7): 1361-1369. 46 GainorJF, Sequist LV, Shaw AT, et al. Clinical correlation and frequency of programmed death ligand-1 (PD-L1) expression in EGFR-mutant and A LK-rearranged non-small cell lung cancer (NSCLC). J Clin Oncol, 2015, 33(suppl): abstr 8012. 47 Chen N, Fang W, Zhan J, et al. Up-regulation of PD-L1 by egfr activation mediates the immune escape in EGFR-driven NSCLC: Implication for optional immune targeted therapy for NSCLC patients with EGFR mutation. J Thorac Oncol, 2015, 10(6): 910-923. 48 Riz v i NA , Hel l ma n n M D, Snyder A , et al. Ca ncer i m mu nolog y. Mutational landscape determines sensitivity to PD-1 blockade in non￾small cell lung cancer. Science, 2015, 348(6230): 124-128. 49 Huard B, Gaulard P, Faure F, et al. Cellular ex pression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand. Immunogenetics, 1994, 39(3): 213-217. 50 Triebel F, Jitsukawa S, Baixeras E, et al. LAG-3, a novel lymphocyte activation gene closely related to CD4. J Ex p Med, 1990, 171(5): 1393-1405. 51 Kisielow M, K isielow J, Capoferri-Sollami G, et al. Ex pression of