Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Determinants of immunological evasion and immunocheckpoint inhibition response in non-small cell lung cancer: the genetic front


The incorporation into clinical practice of immune-checkpoint inhibitors (ICIs), such as those targeting the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) and its ligand (PD-L1), has represented a major breakthrough in non-small cell lung cancer (NSCLC) treatment, especially in cases where the cancer has no druggable genetic alterations. Despite becoming the standard of care in certain clinical settings, either alone or in combination with chemotherapy, a proportion of patients do not respond while others actually progress during treatment. Therefore, there is a clinical need to identify accurate predictive biomarkers and to develop novel therapeutic strategies based on ICIs. Although they have limitations, the current markers evaluated to select which patients will undergo ICI treatment are the levels of PD-L1 and the tumor mutational burden. In this paper we describe what is currently known about the dynamic interaction between the cancer cell and the immune system during carcinogenesis, with a particular focus on the description of the functions and gene alterations that preclude the host immunoresponse in NSCLC. We emphasize the deleterious gene alterations in components of the major histocompatibility complex (HLA-I or B2M) and of the response to IFNγ (such as JAK2) which are mutually exclusive and can affect up to one fifth of the NSCLCs. The participation of other gene alterations, such as those of common oncogenes and tumor suppressors, and of the epigenetic alterations will also be discussed, in detail. Finally, we discuss the potential use of the tumor’s genetic profile to predict sensitivity to ICIs.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. 1.

    Burnet M. Cancer - A biological approach. Br Med J. 1957;1:841–7.

    CAS  Article  Google Scholar 

  2. 2.

    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    CAS  Article  Google Scholar 

  3. 3.

    Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.

    CAS  Article  Google Scholar 

  4. 4.

    Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275–87.

    CAS  Article  Google Scholar 

  5. 5.

    Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.

    CAS  Article  Google Scholar 

  6. 6.

    Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7:596–609.

    CAS  Article  Google Scholar 

  7. 7.

    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.

    CAS  Article  Google Scholar 

  8. 8.

    Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.

    CAS  Article  Google Scholar 

  9. 9.

    Tsao MS, Kerr KM, Dacic S, Yatabe Y, Hirsch FR. IASLC Atlas of PD-L1 testing in lung cancer. (2017)

  10. 10.

    Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069–108.

    Article  Google Scholar 

  11. 11.

    Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    CAS  Article  Google Scholar 

  12. 12.

    Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han JY, 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;387:1540–50.

    CAS  Article  Google Scholar 

  13. 13.

    Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255–65.

    Article  Google Scholar 

  14. 14.

    Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.

    CAS  Article  Google Scholar 

  15. 15.

    Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-line Nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376:2415–26.

    CAS  Article  Google Scholar 

  16. 16.

    Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379:2040–51.

    CAS  Article  Google Scholar 

  17. 17.

    Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078–92.

    CAS  Article  Google Scholar 

  18. 18.

    Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301.

    CAS  Article  Google Scholar 

  19. 19.

    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379:2342–50.

    CAS  Article  Google Scholar 

  20. 20.

    Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, Borghaei H, Brahmer JR, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017;18:31–41.

    CAS  Article  Google Scholar 

  21. 21.

    Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Supplement 4):iv192–237.

    CAS  Article  Google Scholar 

  22. 22.

    Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay 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;23:1920–198.

    CAS  Article  Google Scholar 

  23. 23.

    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;23:4242–50.

    CAS  Article  Google Scholar 

  24. 24.

    Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197–218.

    CAS  Article  Google Scholar 

  25. 25.

    Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018;362.

    Article  Google Scholar 

  26. 26.

    Voron T, Colussi O, Marcheteau E, Pernot S, Nizard M, Pointet AL, et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+T cells in tumors. J Exp Med. 2015;212:139–48.

    CAS  Article  Google Scholar 

  27. 27.

    Johnston CJC, Smyth DJ, Dresser DW, Maizels RM. TGF-β in tolerance, development and regulation of immunity. Cell Immunol. 2016;299:14–22.

    CAS  Article  Google Scholar 

  28. 28.

    Pereira C, Gimenez-Xavier P, Pros E, Pajares MJ, Moro M, Gomez A, et al. Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition. Clin Cancer Res. 2017;23:3203–13.

    CAS  Article  Google Scholar 

  29. 29.

    Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol. 2016;34:1223–30.

    CAS  Article  Google Scholar 

  30. 30.

    Donnem T, Hald SM, Paulsen E-E, Richardsen E, Al-Saad S, Kilvaer TK, et al. Stromal CD8+T-cell density, a promising supplement to TNM staging in non-small cell lung cancer. Clin Cancer Res. 2015;21:2635–43.

    Article  Google Scholar 

  31. 31.

    O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16:151–67.

    Article  Google Scholar 

  32. 32.

    Springer S. Transport and quality control of MHC class I molecules in the early secretory pathway. Curr Opin Immunol. 2015;34:83–90.

    CAS  Article  Google Scholar 

  33. 33.

    Shukla SA, Rooney MS, Rajasagi M, Tiao G, Dixon PM, Lawrence MS, et al. Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes. Nat Biotechnol. 2015;33:1152–8.

    CAS  Article  Google Scholar 

  34. 34.

    Palomero T, Couronné L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA FYN kinase Peripher T cell lymphomas. Nat Genet. 2014;46:166–70.

    CAS  Article  Google Scholar 

  35. 35.

    Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mmutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819–29.

    CAS  Article  Google Scholar 

  36. 36.

    Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, et al. Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung cancer. Cancer Discov. 2017;7:1420–35.

    CAS  Article  Google Scholar 

  37. 37.

    Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6:836–48.

    CAS  Article  Google Scholar 

  38. 38.

    Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13:95–109.

    CAS  Article  Google Scholar 

  39. 39.

    Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA. 1998;95:7556–61.

    CAS  Article  Google Scholar 

  40. 40.

    Ribas A. Releasing the brakes on cancer immunotherapy. N Engl J Med. 2015;373:1490–92.

    Article  Google Scholar 

  41. 41.

    Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, Kalbasi A, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 2017;7:188–201.

    CAS  Article  Google Scholar 

  42. 42.

    Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell. 2016;167:397–404.

    CAS  Article  Google Scholar 

  43. 43.

    Saigi M, Alburquerque-Bejar JJ, Mc Leer-Florin A, Pereira C, Pros E, Romero OA, et al. MET-oncogenic and JAK2-Inactivating alterations are independent factors that affect regulation of PD-L1 expression in lung cancer. Clin Cancer Res. 2018;24:4579–87.

    CAS  Article  Google Scholar 

  44. 44.

    Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127:2930–40.

    Article  Google Scholar 

  45. 45.

    Ikeda S, Okamoto T, Okano S, Umemoto Y, Tagawa T, Morodomi Y, et al. PD-L1 is upregulated by simultaneous amplification of the PD-L1 and JAK2 genes in non-small cell lung cancer. J Thorac Oncol. 2016;11:62–71.

    Article  Google Scholar 

  46. 46.

    Goodman AM, Piccioni D, Kato S, Boichard A, Wang H-Y, Frampton G, et al. Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid tumors. JAMA Oncol. 2018;4:1237–44.

    Article  Google Scholar 

  47. 47.

    Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Nagano S, et al. Aberrant PD-L1 expression through 3’-UTR disruption in multiple cancers. Nature. 2016;534:402–6.

    CAS  Article  Google Scholar 

  48. 48.

    Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8.

    CAS  Article  Google Scholar 

  49. 49.

    Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377:2500–1.

    Article  Google Scholar 

  50. 50.

    Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.

    CAS  Article  Google Scholar 

  51. 51.

    Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8.

    CAS  Article  Google Scholar 

  52. 52.

    Swanton C, McGranahan N, Starrett GJ, Harris RS. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 2015;5:704–12.

    CAS  Article  Google Scholar 

  53. 53.

    Wang S, Jia M, He Z. Liu X-S. APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer. Oncogene. 2018;37:3924–36.

    CAS  Article  Google Scholar 

  54. 54.

    Hellmann MD, Ciuleanu T-E, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378:2093–104.

    CAS  Article  Google Scholar 

  55. 55.

    Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, et al. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell. 2018;33:843–52.

    CAS  Article  Google Scholar 

  56. 56.

    Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 2002;62:3659–62.

    CAS  PubMed  Google Scholar 

  57. 57.

    Sanchez-Cespedes M. A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene. 2007;26:7825–32.

    CAS  Article  Google Scholar 

  58. 58.

    Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Mäkelä TP, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol. 2003;2:28.

    Article  Google Scholar 

  59. 59.

    Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, et al. STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell activity in the lung tumor microenvironment. Cancer Res. 2016;76:999–1008.

    CAS  Article  Google Scholar 

  60. 60.

    Ihara S, Kida H, Arase H, Tripathi LP, Chen YA, Kimura T, et al. Inhibitory roles of signal transducer and activator of transcription 3 in antitumor immunity during carcinogen-induced lung tumorigenesis. Cancer Res. 2012;72:2990–9.

    CAS  Article  Google Scholar 

  61. 61.

    Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 2015;8:860–77.

    Article  Google Scholar 

  62. 62.

    Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8:822–35.

    CAS  Article  Google Scholar 

  63. 63.

    Kitajima S, Ivanova E, Guo S, Yoshida R, Campisi M, Sundararaman SK, et al. Suppression of STING Associated with LKB1 loss in KRAS-driven lung cancer. Cancer Discov. 2019;9:34–45.

    Article  Google Scholar 

  64. 64.

    Romero OA, Sanchez Cespedes M. The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene. 2014;33:2681–9.

    CAS  Article  Google Scholar 

  65. 65.

    Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay RE, Luoma AM, et al. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science. 2018;359:770–5.

    CAS  Article  Google Scholar 

  66. 66.

    Gainor JF, Shaw AT, Sequist LV, Fu X, Azzoli CG, Piotrowska Z, et al. EGFR Mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22:4585–93.

    CAS  Article  Google Scholar 

  67. 67.

    Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5:850–9.

    CAS  Article  Google Scholar 

  68. 68.

    Sabari JK, Leonardi GC, Shu CA, Umeton R, Montecalvo J, Ni A, et al. PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Ann Oncol. 2018;29:2085–91.

    CAS  Article  Google Scholar 

  69. 69.

    Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6:202–16.

    CAS  Article  Google Scholar 

  70. 70.

    Best SA, De Souza DP, Kersbergen A, Policheni AN, Dayalan S, Tull D, et al. Synergy between the KEAP1/NRF2 and PI3K pathways drives non-small-cell lung cancer with an altered immune microenvironment. Cell Metab. 2018;27:935–43.

    CAS  Article  Google Scholar 

  71. 71.

    Kerdidani D, Chouvardas P, Arjo AR, Giopanou I, Ntaliarda G, Guo YA, et al. Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma. Nat Commun. 2019;10:1405.

    Article  Google Scholar 

  72. 72.

    He Y, Cao J, Zhao C, Li X, Zhou C, Hirsch FR. TIM-3, a promising target for cancer immunotherapy. Onco Targets Ther. 2018;11:7005–9.

    Article  Google Scholar 

  73. 73.

    Duruisseaux M, Martínez-Cardús A, Calleja-Cervantes ME, Moran S, Castro de Moura M, Davalos V, et al. Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicentre, retrospective analysis. Lancet Respir Med. 2018;6:771–81.

    CAS  Article  Google Scholar 

  74. 74.

    Vendetti FP, Topper M, Huang P, Dobromilskaya I, Easwaran H, Wrangle J, et al. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget. 2014;6:56–70.

    PubMed Central  Google Scholar 

  75. 75.

    Adeegbe DO, Liu Y, Lizotte PH, Kamihara Y, Aref AR, Almonte C, et al. Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer. Cancer Discov. 2017;7:852–67.

    CAS  Article  Google Scholar 

  76. 76.

    Zingg D, Arenas-Ramirez N, Sahin D, Rosalia RA, Antunes AT, Haeusel J, et al. The histone methyltransferase EZH2 controls mechanisms of adaptive resistance to tumor immunotherapy. Cell Rep. 2017;20:854–67.

    CAS  Article  Google Scholar 

  77. 77.

    Cañadas I, Thummalapalli R, Kim JW, Kitajima S, Jenkins RW, Christensen CL, et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat Med. 2018;24:1143–50.

    Article  Google Scholar 

  78. 78.

    Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018;36:633–41.

    CAS  Article  Google Scholar 

  79. 79.

    Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, et al. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer-a meta-analysis. J Thorac Oncol. 2017;12:403–7.

    Article  Google Scholar 

  80. 80.

    Roach C, Zhang N, Corigliano E. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol. 2016;24:392–7.

    CAS  Article  Google Scholar 

  81. 81.

    Fabrizio DA, Milbury C, Yip WK, Ramamurthy X, Bai V, Pattani P, et al. Analytic validation of tumor mutational burden as a companion diagnostic for combination immunotherapy in non-small lung cancer. Ann Oncol. 2018;29 (Suppl 8):viii14–viii57.

    Google Scholar 

Download references


This work was supported by Spanish grant SAF2014-54571-R (to MSC) from the MINECO and a grant from the Fundación Científica Asociación Española Contra el Cancer-GCB14142170MONT. Saigi is supported by a Rio Hortega (CM17/00180) contract. We also thank the CERCA program for support.

Author information



Corresponding author

Correspondence to Montse Sanchez-Cespedes.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saigi, M., Alburquerque-Bejar, J.J. & Sanchez-Cespedes, M. Determinants of immunological evasion and immunocheckpoint inhibition response in non-small cell lung cancer: the genetic front. Oncogene 38, 5921–5932 (2019).

Download citation


Quick links