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Lung Cancer pp 203–223Cite as

Immunotherapy in Lung Cancer

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 170))

Abstract

Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient’s innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

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References

  1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van ‘t Veer L, Vincent-Salomon A, Waddell N, Yates LR, Australian Pancreatic Cancer Genome I, Consortium IBC, Consortium IM-S, PedBrain I, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR (2013) Signatures of mutational processes in human cancer. Nature 500 (7463):415–421. doi:10.1038/nature12477

    Google Scholar 

  2. Antonia SJ, Brahmer JR, Gettinger S, Chow LQ, Juergens R, Shepherd FA, Laurie SA, Gerber DE, Goldman J, Shen R, Harbison C, Chen AC, Borghaei H, Rizvi NA (2014) Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer (NSCLC). In: Chicago multidisciplinary symposium in thoracic oncology, Chicago, IL (vol 5). International Jounral of Radiation Oncology, p S2

    Google Scholar 

  3. Antonia SJ GS, Balmanoukian A, Sanborn RE, Steele KE, Narwal R, Robbins PB, Gu Y, Karakunnel JJ, Rizvi N (2015) Phase 1b study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients with advanced non-small cell lung cancer (NSCLC). In: American Society of clinical oncology annual meeting, Chicago, IL

    Google Scholar 

  4. Antonia SJ GS, Chow LQM, Juergens RA, Borghaei H, et al (2014) Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: Interim phase I results. In: ASCO annual meeting

    Google Scholar 

  5. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. The New England journal of medicine 373(2):123–135. doi:10.1056/NEJMoa1504627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Brahmer JR Horn L, Antonia SJ, et al (2013) Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. In: World conference on lung cancer

    Google Scholar 

  7. Brahmer JR, Pardoll DM (2013) Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer immunology research 1(2):85–91. doi:10.1158/2326-6066.CIR-13-0078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brahmer JR Rizvi NA, Luzky J, Khleif S, Blake-Haskins A, et al (2014) Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC. In: ASCO annual meeting

    Google Scholar 

  9. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. The New England journal of medicine 366(26):2455–2465. doi:10.1056/NEJMoa1200694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquee L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE, Helwig C, Schroder A, Shepherd FA, team St (2014) Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. The Lancet Oncology 15(1):59-68. doi:10.1016/S1470-2045(13)70510-2

    Google Scholar 

  11. D’Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, Tibaldi C, Minuti G, Salvini J, Coppi E, Chella A, Fontanini G, Filice ME, Tornillo L, Incensati RM, Sani S, Crino L, Terracciano L, Cappuzzo F (2015) PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 112(1):95–102. doi:10.1038/bjc.2014.555

    Article  PubMed  Google Scholar 

  12. Di Giacomo AM, Biagioli M, Maio M (2010) The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Semin Oncol 37(5):499–507. doi:10.1053/j.seminoncol.2010.09.007

    Article  PubMed  Google Scholar 

  13. Diefenbach A, Raulet DH (2002) The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev 188:9–21

    Article  CAS  PubMed  Google Scholar 

  14. Domagala-Kulawik J (2015) The role of the immune system in non-small cell lung carcinoma and potential for therapeutic intervention. Translational lung cancer research 4(2):177–190. doi:10.3978/j.issn.2218-6751.2015.01.11

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4(1):11–22. doi:10.1038/nrc1252

    Article  CAS  PubMed  Google Scholar 

  16. Finn OJ (2008) Cancer immunology. The New England journal of medicine 358(25):2704–2715. doi:10.1056/NEJMra072739

    Article  CAS  PubMed  Google Scholar 

  17. Finn OJ (2012) Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of oncology: Official Journal of the European Society for Medical Oncology/ESMO 23(Suppl 8:viii6–viii9. doi:10.1093/annonc/mds256

    Google Scholar 

  18. Garon EB GL, Rizvi N, Hui R, Balmanoukian AS, Patnaik A, et al (2014) Antitumor activity of pembrolizumab (Pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of patients (pts) with advanced non-small cell lung carcinoma (NSCLC). In: European Society for medical oncology 2014 congress, Madrid, Spain

    Google Scholar 

  19. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K- (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. New Engl J Med 372(21):2018–2028. doi:10.1056/NEJMoa1501824

    Article  PubMed  Google Scholar 

  20. Gettinger SN, Kowanetz M, Koeppen H., Wistuba II, et al (2015) Molecular, immune and histopathological characterization of NSCLC based on PDL1 expression on tumor and immune cells and association with response to the anti-PDL1 antibody MPDL3280A. In: American Society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  21. Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR (2015) 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: Official J Am Soc Clin Oncol 33(18):2004–2012. doi:10.1200/JCO.2014.58.3708

    Article  CAS  Google Scholar 

  22. Goldberg SM, Gettinger SN, Mahajan A, et al (2015) Activity and safety of pembrolizumab in patients with metastatic non-small cell lung cancer with untreated brain metastases. In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  23. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150(6):1121–1134. doi:10.1016/j.cell.2012.08.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ, Altorki NK (2005) Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res: Official J Am Assoc Cancer Res 11(22):8055–8062. doi:10.1158/1078-0432.CCR-05-1203

    Article  CAS  Google Scholar 

  25. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  26. Hellmann MD, Creelan BC, Sima CS, Iams WT, Antonia SJ, Horn L, Brahmer JR, Gettinger S, Harbison C, Rizvi N (2014) Smoking history and response to nivolumab in patients with advanced NSCLCs. In: Annals of Oncology (Supplement 4, pp iv426–iv470)

    Google Scholar 

  27. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567. doi:10.1038/nature14011

    Article  CAS  PubMed  Google Scholar 

  28. Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, Itoh T, Ohbuchi T, Kondo S, Katoh H (2006) Concurrent infiltration by CD8+T cells and CD4+T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 94(2):275–280. doi:10.1038/sj.bjc.6602934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hirasawa Y, Kohno N, Yokoyama A, Kondo K, Hiwada K, Miyake M (2000) Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer. Am J Respir Crit Care Med 161(2 Pt 1):589–594. doi:10.1164/ajrccm.161.2.9905028

    Article  CAS  PubMed  Google Scholar 

  30. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. New England J Med 363(8):711–723. doi:10.1056/NEJMoa1003466

    Article  CAS  Google Scholar 

  31. Horn L Horn R, Spigel DR, et al (2013) An analysis of the relationship of clinical activity to baseline EGFR status, PD-L1 expression and prior treatment history in patients with non-small cell lung cancer (NSCLC) following PD-L1 blockade with MPDL3280A (anti-PDL1). In: World conference on lung cancer

    Google Scholar 

  32. Howell M, Lee R, Bowyer S, Fusi A, Lorigan P (2015) Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer. Lung Cancer 88(2):117–123. doi:10.1016/j.lungcan.2015.02.007

    Article  PubMed  Google Scholar 

  33. Ibrahim R, Berman D, DePril V, Humphrey R, Chen T (2011) Ipilimumab safety profile: summary of findings from completed trials in advanced melanoma. In: American society of clinical oncology annual meeting

    Google Scholar 

  34. Ikeda S, Funakoshi N, Inagaki M, Shibata T (2006) Clinicopathologic roles of tumor-infiltrating lymphocytes and CD8-positive lymphocytes in lung cancer imprint smears in squamous cell carcinoma and adenocarcinoma. Acta Cytol 50(4):423–429

    Article  PubMed  Google Scholar 

  35. Johnson DB, Peng C, Sosman JA (2015) Nivolumab in melanoma: latest evidence and clinical potential. Ther Adv Med Oncol 7(2):97–106. doi:10.1177/1758834014567469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Johnson DB, Rioth MJ, Horn L (2014) Immune checkpoint inhibitors in NSCLC. Curr Treat Options Oncol 15(4):658–669. doi:10.1007/s11864-014-0305-5

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ju S, Qiu H, Zhou X, Zhu B, Lv X, Huang X, Li J, Zhang Y, Liu L, Ge Y, Johnson DE, Ju S, Shu Y (2009) CD13 + CD4 + CD25hi regulatory T cells exhibit higher suppressive function and increase with tumor stage in non-small cell lung cancer patients. Cell Cycle 8(16):2578–2585

    Article  CAS  PubMed  Google Scholar 

  38. Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704. doi:10.1146/annurev.immunol.26.021607.090331

    Article  CAS  PubMed  Google Scholar 

  39. Kerr KM, Tsao M-S, Nicholson A, Yasushi Y, Wistuba II, Hirsch FR (2015) Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art? J Thoracic Oncol 10(7):985–989

    Google Scholar 

  40. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. New England J Med. doi:10.1056/NEJMoa1504030

    Google Scholar 

  41. Lesokhin AM, Callahan MK, Postow MA, Wolchok JD (2015) On being less tolerant: enhanced cancer immunosurveillance enabled by targeting checkpoints and agonists of T cell activation. Sci Trans Med 7(280):280sr281. doi:10.1126/scitranslmed.3010274

    Google Scholar 

  42. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M (2012) Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol: Official J Am Soc Clin Oncol 30(17):2046–2054. doi:10.1200/JCO.2011.38.4032

    Article  CAS  Google Scholar 

  43. Mittal D, Gubin MM, Schreiber RD, Smyth MJ (2014) New insights into cancer immunoediting and its three component phases–elimination, equilibrium and escape. Curr Opin Immunol 27:16–25. doi:10.1016/j.coi.2014.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mu CY, Huang JA, Chen Y, Chen C, Zhang XG (2011) High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 28(3):682–688. doi:10.1007/s12032-010-9515-2

    Article  CAS  PubMed  Google Scholar 

  45. Papadimitrakopoulou V, Patnaik A, Borghaei H, et al (2015). Pembrolizumab (pembro; MK-3475) plus platinum doublet chemotherapy (PDC) as front-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 Cohorts A and C. In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  46. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264. doi:10.1038/nrc3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Patnaik A, Socinski MA, Gubens MA, et al (2015) Phase 1 study of pembrolizumab (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D. In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  48. Paz-Ares L Horn L, Borghaei H, Spigel DR, et al (2015) Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). In: American society of clinical oncology annual meeting, Chicago, IL, 2015. J Clin Oncol

    Google Scholar 

  49. Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr, Patz EF Jr (2006) Tumor infiltrating Foxp3 + regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 107(12):2866–2872. doi:10.1002/cncr.22282

    Article  PubMed  Google Scholar 

  50. Ramlogan-Steel CA, Steel JC, Morris JC (2014) Lung cancer vaccines: current status and future prospects. Trans Lung Cancer Res 3(1):46–52. doi:10.3978/j.issn.2218-6751.2013.12.01

    CAS  Google Scholar 

  51. Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Annals Oncol: Official J Eur Soc Med Oncol/ESMO 24(1):75–83. doi:10.1093/annonc/mds213

    Article  CAS  Google Scholar 

  52. Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, Garbe C, Gogas H, Schachter J, Linette G, Lorigan P, Kendra KL, Maio M, Trefzer U, Smylie M, McArthur GA, Dreno B, Nathan PD, Mackiewicz J, Kirkwood JM, Gomez-Navarro J, Huang B, Pavlov D, Hauschild A (2013) Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol: Official J Am Soc Clin Oncol 31(5):616–622. doi:10.1200/JCO.2012.44.6112

    Article  CAS  Google Scholar 

  53. Ribas A, Robert C, Hodi FS, Wolchok JD, et al. printer-friendly version. Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature. In: American society of clinical oncology annual meeting, Chicago, IL, 2015. J Clin Oncol

    Google Scholar 

  54. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015a) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348(6230):124–128. doi:10.1126/science.aaa1348

    Google Scholar 

  55. Rizvi NA, Man Chow LQ, Borghaei H, Shen Y, Harbison C, Alaparthy S, Chen AC, Gettinger S (2014) Safety and response with nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus erlotinib in patients (pts) with epidermal growth factor receptor mutant (EGFR MT) advanced NSCLC (vol 5s). In: American society of clinical oncology annual meeting, Chicago, IL. J Clin ONcol

    Google Scholar 

  56. Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS (2015b) 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. The Lancet Oncology 16 (3):257-265. doi:10.1016/S1470-2045(15)70054-9

    Google Scholar 

  57. Rizvi NA Shepherd FA, Antonia SJ, Brahmer JR, Chow LQ, Goldman J, et al (2014) First-line monotherapy with nivolumab (anti-PD-1; BMS-936558, ONO-4538) in advanced non-small cell lung cancer (NSCLC): safety, efficacy and correlation of outcomes with PD-L1 status. Int J Radiat Oncol

    Google Scholar 

  58. Ruffini E, Asioli S, Filosso PL, Lyberis P, Bruna MC, Macri L, Daniele L, Oliaro A (2009) Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Annals Thorac Surgery 87(2):365–371; discussion 371–362. doi:10.1016/j.athoracsur.2008.10.067

    Google Scholar 

  59. Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T, Srinivasan M, Korman AJ (2013) Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer immunology research 1(1):32–42. doi:10.1158/2326-6066.CIR-13-0013

    Article  CAS  PubMed  Google Scholar 

  60. Sienel W, Varwerk C, Linder A, Kaiser D, Teschner M, Delire M, Stamatis G, Passlick B (2004) Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study. Eur J Cardiothorac Surg 25(1):131–134

    Article  CAS  PubMed  Google Scholar 

  61. Smyth MJ, Dunn GP, Schreiber RD (2006) Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 90:1–50. doi:10.1016/S0065-2776(06)90001-7

    Article  CAS  PubMed  Google Scholar 

  62. Soria JC et al (2013) Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). In: ECCO annual congress

    Google Scholar 

  63. Soria JC, Marabelle A, Brahmer JR, Gettinger S (2015) Immune checkpoint modulation for non-small cell lung cancer. Clinical Cancer Res: Official J Am Assoc Cancer Res 21(10):2256–2262. doi:10.1158/1078-0432.CCR-14-2959

    Article  CAS  Google Scholar 

  64. Spigel DR Chart JE, Gettinger SN, Chao BH, et al (2015) 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). In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  65. Spira A.I. Park K, Mazieres J, Vansteenkiste JF, et al (2015) Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  66. Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF (2013) Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 5(200):200ra116. doi:10.1126/scitranslmed.3006504

    Google Scholar 

  67. Sundar R, Cho BC, Brahmer JR, Soo RA (2015) Nivolumab in NSCLC: latest evidence and clinical potential. Therapeutic advances in medical oncology 7(2):85–96. doi:10.1177/1758834014567470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res: Official J Am Assoc Cancer Res 20(19):5064–5074. doi:10.1158/1078-0432.CCR-13-3271

    Article  CAS  Google Scholar 

  69. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New England J Med 366(26):2443–2454. doi:10.1056/NEJMoa1200690

    Article  CAS  Google Scholar 

  70. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528):568–571. doi:10.1038/nature13954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Tyagi P, Mirakhur B (2009) MAGRIT: the largest-ever phase III lung cancer trial aims to establish a novel tumor-specific approach to therapy. Clin Lung Cancer 10(5):371–374. doi:10.3816/CLC.2009.n.052

    Article  PubMed  Google Scholar 

  72. Vansteenkiste J, Cho B, Vanakesa T, De Pase T, et al (2014) MAGRIT, a double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of the recMAGE-A3 + AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC). In: European society of medical oncology, Madrid, Spain

    Google Scholar 

  73. Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, Lopez-Brea M, Vanakesa T, Jassem J, Kalofonos H, Perdeus J, Bonnet R, Basko J, Janilionis R, Passlick B, Treasure T, Gillet M, Lehmann FF, Brichard VG (2013) Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol: Official J Am Soc Clin Oncol 31(19):2396–2403. doi:10.1200/JCO.2012.43.7103

    Article  CAS  Google Scholar 

  74. Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol: Official J Am Soc Clin Oncol 30(21):2691–2697. doi:10.1200/JCO.2012.41.6750

    Article  CAS  Google Scholar 

  75. Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res: Official J Am Assoc Cancer Res 15(23):7412–7420. doi:10.1158/1078-0432.CCR-09-1624

    Article  CAS  Google Scholar 

  76. Wolchok JD, Saenger Y (2008) The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation. Oncologist 13(Suppl 4):2–9. doi:10.1634/theoncologist.13-S4-2

    Article  CAS  PubMed  Google Scholar 

  77. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61(12):4766–4772

    CAS  PubMed  Google Scholar 

  78. Xia W, Wang J, Xu Y, Jiang F, Xu L (2014) L-BLP25 as a peptide vaccine therapy in non-small cell lung cancer: a review. J Thorac Dis 6(10):1513–1520. doi:10.3978/j.issn.2072-1439.2014.08.17

    PubMed  PubMed Central  Google Scholar 

  79. Zatloukal P, Heo DS, Park K, Kang J, Butts C, Bradford D, Graziano S, Huang B, Healey D (2009) Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC). In: American society of clinical oncology annual meeting, Chicago, IL. J Clin Oncol

    Google Scholar 

  80. Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307. doi:10.1038/nri1806

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Hematology/Oncology, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 37232, USA

    Emily H. Castellanos & Leora Horn

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    Karen L. Reckamp

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Castellanos, E.H., Horn, L. (2016). Immunotherapy in Lung Cancer. In: Reckamp, K. (eds) Lung Cancer. Cancer Treatment and Research, vol 170. Springer, Cham. https://doi.org/10.1007/978-3-319-40389-2_10

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