Immunotherapy landscape of non-small cell lung cancer_West China Medical Journal

Authors：

 ZHANG Li

Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P. R. China;

Corresponding author：

ZHANG Li, Email: zhanglipumch@aliyun.com

Keywords：

Non-small cell lung cancer; Checkpoint inhibitor; Biomarker; Immune resistance

DOI：

10.7507/1002-0179.201803213

Video：

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As emerging means of cancer treatment, immunotherapy is the fourth major therapeutic strategy after surgery, chemoradiotherapy, and targeted therapy, which benefits patients a lot. It has been more than 100 years for the medical community exploring how to harness the immune system to fight cancer. Since the advent of ipilimumab in 2011, the first checkpoint inhibitor, cancer immunotherapy represented by checkpoint inhibitors has exploded. Several programmed death protein-1 and programmed cell death ligand-1 inhibitors have successively been approved to treat advanced non-small cell lung cancer in the second-line setting or even the first-line setting. But checkpoint inhibitors therapy has only achieved limited benefit at the present stage. Exploring potential predictive biomarkers and mechanisms of resistance are in need of further consideration to optimize immunotherapy.

Citation： ZHANG Li. Immunotherapy landscape of non-small cell lung cancer. West China Medical Journal, 2018, 33(4): 375-378. doi: 10.7507/1002-0179.201803213 Copy

1.	Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J, 1992, 11(11): 3887-3895.
2.	Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 1999, 11(2): 141-151.
3.	Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001, 291(552): 319-322.
4.	Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med, 1999, 5(12): 1365-1369.
5.	Tseng SY, Otsuji M, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med, 2001, 193(7): 839-846.
6.	Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med, 2002, 8(8): 793-800.
7.	Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med, 2015, 373(17): 1627-1639.
8.	Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med, 2015, 373(2): 123-135.
9.	Herbst RS, Baas P, Kim DW, 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(127): 1540-1550.
10.	Rittmeyer A, Barlesi F, Waterkamp D, 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(166): 255-265.
11.	Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer. N Engl J Med, 2017, 377(20): 1919-1929.
12.	Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
13.	Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol, 2016, 17(11): 1497-1508.
14.	Rizvi NA, Hellmann MD, Brahmer JR, et al. Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol, 2016, 34(25): 2969-2679.
15.	Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013, 39(1): 1-10.
16.	Blumenthal GM, Theoret MR, Pazdur R. Treatment beyond progression with immune checkpoint inhibitors-known unknowns. JAMA Oncol, 2017, 3(11): 1473-1474.
17.	Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science, 2015, 350(6264): 1084-1089.
18.	Gopalakrishnan V, Spencer C, Reuben A, et al. Abstract 2672: response to anti-PD-1 based therapy in metastatic melanoma patients is associated with the diversity and composition of the gut microbiome. Cancer Res, 2017, 77(13 Suppl): 2672.
19.	Saleh K, Khalife-saleh N, Kourie HR. Is gut microbiome a predictive marker to response to immune checkpoint inhibitors? Immunotherapy, 2017, 9(11): 865-866.
20.	Anichini A, Tassi E, Grazia G, et al. The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy. Cancer Immunol Immunother, 2018. https://doi.org/10.1007/s00262-018-2147-7.
21.	Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med, 2018, 378(2): 158-168.
22.	Kimura H, Tounai Y, Nagato K, et al. A case of heart failure after treatment with anti-PD-1 antibody followed by adoptive transfer of cytokine-activated killer cells in a recurrent lung cancer patient. J Thorac Oncol, 2017, 12(8): e128-e130.
23.	Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med, 2016, 375(18): 1749-1755.
24.	Sharma P, Hu-Lieskovan S, Wargo JA. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell, 2017, 168(4): 707-723.
25.	Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by Anti-PD-1/PD-L1. Clin Cancer Res, 2017, 23(8): 1920-1928.
26.	Kato S, Goodman A, Walavalkar V, et al. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res, 2017, 23(15): 4242-4250.

1. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J, 1992, 11(11): 3887-3895.
2. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 1999, 11(2): 141-151.
3. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001, 291(552): 319-322.
4. Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med, 1999, 5(12): 1365-1369.
5. Tseng SY, Otsuji M, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med, 2001, 193(7): 839-846.
6. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med, 2002, 8(8): 793-800.
7. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med, 2015, 373(17): 1627-1639.
8. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med, 2015, 373(2): 123-135.
9. Herbst RS, Baas P, Kim DW, 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(127): 1540-1550.
10. Rittmeyer A, Barlesi F, Waterkamp D, 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(166): 255-265.
11. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer. N Engl J Med, 2017, 377(20): 1919-1929.
12. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
13. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol, 2016, 17(11): 1497-1508.
14. Rizvi NA, Hellmann MD, Brahmer JR, et al. Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol, 2016, 34(25): 2969-2679.
15. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013, 39(1): 1-10.
16. Blumenthal GM, Theoret MR, Pazdur R. Treatment beyond progression with immune checkpoint inhibitors-known unknowns. JAMA Oncol, 2017, 3(11): 1473-1474.
17. Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science, 2015, 350(6264): 1084-1089.
18. Gopalakrishnan V, Spencer C, Reuben A, et al. Abstract 2672: response to anti-PD-1 based therapy in metastatic melanoma patients is associated with the diversity and composition of the gut microbiome. Cancer Res, 2017, 77(13 Suppl): 2672.
19. Saleh K, Khalife-saleh N, Kourie HR. Is gut microbiome a predictive marker to response to immune checkpoint inhibitors? Immunotherapy, 2017, 9(11): 865-866.
20. Anichini A, Tassi E, Grazia G, et al. The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy. Cancer Immunol Immunother, 2018. https://doi.org/10.1007/s00262-018-2147-7.
21. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med, 2018, 378(2): 158-168.
22. Kimura H, Tounai Y, Nagato K, et al. A case of heart failure after treatment with anti-PD-1 antibody followed by adoptive transfer of cytokine-activated killer cells in a recurrent lung cancer patient. J Thorac Oncol, 2017, 12(8): e128-e130.
23. Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med, 2016, 375(18): 1749-1755.
24. Sharma P, Hu-Lieskovan S, Wargo JA. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell, 2017, 168(4): 707-723.
25. Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by Anti-PD-1/PD-L1. Clin Cancer Res, 2017, 23(8): 1920-1928.
26. Kato S, Goodman A, Walavalkar V, et al. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res, 2017, 23(15): 4242-4250.

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