Skip to main content Accessibility help
Hostname: page-component-5c569c448b-r8t2r Total loading time: 0.479 Render date: 2022-07-01T18:39:06.626Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

Cancer mutation profiles predict ICIs efficacy in patients with non-small cell lung cancer

Published online by Cambridge University Press:  04 April 2022

Liping Zhu
Department of Medical Oncology, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, Shandong Province, People's Republic of China
Dafu Ye
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
Tianyu Lei
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
Jie Wu
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
Wei Wang*
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
Bin Xu*
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
Author for correspondence: Bin Xu, E-mail:, Wei Wang,
Author for correspondence: Bin Xu, E-mail:, Wei Wang,


Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.

Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



These authors contributed equally.


Samadder, NJ et al. (2021) Comparison of universal genetic testing vs guideline-directed targeted testing for patients with hereditary cancer syndrome. JAMA Oncology 7, 230237.CrossRefGoogle ScholarPubMed
Martinez-Jimenez, F et al. (2020) A compendium of mutational cancer driver genes. Nature Reviews Cancer 20, 555572.CrossRefGoogle ScholarPubMed
Thomas, RK et al. (2007) High-throughput oncogene mutation profiling in human cancer. Nature Genetics 39, 347351.CrossRefGoogle ScholarPubMed
Boussiotis, VA (2016) Molecular and biochemical aspects of the PD-1 checkpoint pathway. New England Journal of Medicine 375, 17671778.CrossRefGoogle ScholarPubMed
Lastwika, KJ et al. (2016) Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer. Cancer Research 76, 227238.CrossRefGoogle ScholarPubMed
Zhang, J et al. (2018) Biochemical aspects of PD-L1 regulation in cancer immunotherapy. Trends in Biochemical Sciences 43, 10141032.CrossRefGoogle ScholarPubMed
Roelands, J et al. (2020) Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response. Journal for Immunotherapy of Cancer 8, e000617.CrossRefGoogle Scholar
Wu, J et al. (2020) CMTM Family proteins 1–8: roles in cancer biological processes and potential clinical value. Cancer Biology & Medicine 17, 528542.CrossRefGoogle ScholarPubMed
Chen, DS and Mellman, I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39, 110.CrossRefGoogle ScholarPubMed
Chen, DS and Mellman, I (2017) Elements of cancer immunity and the cancer-immune set point. Nature 541, 321330.CrossRefGoogle ScholarPubMed
Zhao, Y et al. (2021) Oncolytic adenovirus: prospects for cancer immunotherapy. Frontiers in Microbiology 12, 707290.CrossRefGoogle ScholarPubMed
Kelly, PN (2018) The cancer immunotherapy revolution. Science 359, 13441345.CrossRefGoogle ScholarPubMed
Wang, Z et al. (2018) Comutations in DNA damage response pathways serve as potential biomarkers for immune checkpoint blockade. Cancer Research 78, 64866496.CrossRefGoogle ScholarPubMed
Marinelli, D et al. (2020) KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden. Annals of Oncology: Official Journal of the European Society for Medical Oncology 31, 17461754.CrossRefGoogle ScholarPubMed
Pan, D et al. (2021) A gene mutation signature predicting immunotherapy benefits in patients with NSCLC. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 16, 419427.CrossRefGoogle ScholarPubMed
Bai, X et al. (2020) Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study. Journal for Immunotherapy of Cancer 8, e000381.CrossRefGoogle ScholarPubMed
Sun, L et al. (2021) MGA Mutation as a novel biomarker for immune checkpoint therapies in non-squamous non-small cell lung cancer. Frontiers in Pharmacology 12, 625593.CrossRefGoogle ScholarPubMed
Wu, J et al. (2021) A risk model developed based on tumor microenvironment predicts overall survival and associates with tumor immunity of patients with lung adenocarcinoma. Oncogene 40, 44134424.CrossRefGoogle ScholarPubMed
Kumagai, S, Koyama, S and Nishikawa, H (2021) Antitumour immunity regulated by aberrant ERBB family signalling. Nature Reviews Cancer 21, 181197.CrossRefGoogle ScholarPubMed
Siegel, RL, Miller, KD and Jemal, A (2020) Cancer statistics, 2020. CA: a Cancer Journal for Clinicians 70, 730.Google ScholarPubMed
Skoulidis, F and Heymach, JV (2019) Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nature Reviews Cancer 19, 495509.CrossRefGoogle ScholarPubMed
Facchinetti, F et al. (2016) Moving immune checkpoint blockade in thoracic tumors beyond NSCLC. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 11, 18191836.CrossRefGoogle ScholarPubMed
Rudd, CE, Taylor, A and Schneider, H (2009) CD28 And CTLA-4 coreceptor expression and signal transduction. Immunological Reviews 229, 1226.CrossRefGoogle ScholarPubMed
Barber, DL et al. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682687.CrossRefGoogle ScholarPubMed
Xia, L, Liu, Y and Wang, Y (2019) PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: current status and future directions. The Oncologist 24, S31S41.CrossRefGoogle ScholarPubMed
Brahmer, J et al. (2015) Nivolumab versus docetaxel in advanced squamous-cell Non-small-cell lung cancer. New England Journal of Medicine 373, 123135.CrossRefGoogle ScholarPubMed
Fehrenbacher, L et al. (2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387, 18371846.CrossRefGoogle ScholarPubMed
Le, DT et al. (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409413.CrossRefGoogle ScholarPubMed
Le, DT et al. (2015) PD-1 Blockade in tumors with mismatch-repair deficiency. New England Journal of Medicine 372, 25092520.CrossRefGoogle ScholarPubMed
Moreira, L et al. (2012) Identification of lynch syndrome among patients with colorectal cancer. JAMA 308, 15551565.CrossRefGoogle ScholarPubMed
Sargent, DJ et al. (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 28, 32193226.CrossRefGoogle Scholar
Champiat, S et al. (2017) Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clinical Cancer Research 23, 19201928.CrossRefGoogle ScholarPubMed
Reck, M et al. (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. New England Journal of Medicine 375, 18231833.CrossRefGoogle ScholarPubMed
Rittmeyer, A et al. (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389, 255265.CrossRefGoogle ScholarPubMed
Osmani, L et al. (2018) Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): moving from targeted therapy to immunotherapy. Seminars in Cancer Biology 52, 103109.CrossRefGoogle ScholarPubMed
Bodor, JN, Boumber, Y and Borghaei, H (2020) Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer 126, 260270.CrossRefGoogle Scholar
Zhou, J et al. (2018) Programmed death ligand 1 expression and CD8(+) tumor-infiltrating lymphocyte density differences between paired primary and brain metastatic lesions in non-small cell lung cancer. Biochemical and Biophysical Research Communications 498, 751757.CrossRefGoogle ScholarPubMed
Yarchoan, M, Hopkins, A and Jaffee, EM (2017) Tumor mutational burden and response rate to PD-1 inhibition. New England Journal of Medicine 377, 25002501.CrossRefGoogle ScholarPubMed
Rizvi, H et al. (2018) 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. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 36, 633641.CrossRefGoogle ScholarPubMed
Hellmann, MD et al. (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. New England Journal of Medicine 378, 20932104.CrossRefGoogle ScholarPubMed
Hellmann, MD et al. (2018) Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell 33, 843852. e4.CrossRefGoogle ScholarPubMed
Hellmann, MD et al. (2018) Tumor mutational burden and efficacy of Nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33, 853861. e4.CrossRefGoogle ScholarPubMed
Assoun, S et al. (2019) Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer 132, 6571.CrossRefGoogle ScholarPubMed
Gandara, DR et al. (2017) Blood-based biomarkers for cancer immunotherapy: tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L + NSCLC (POPLAR and OAK). Annals of Oncology 28, v460.CrossRefGoogle Scholar
Cabel, L et al. (2018) Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nature Reviews. Clinical Oncology 15, 639650.CrossRefGoogle ScholarPubMed
Guibert, N et al. (2019) Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. Lung Cancer 137, 16.CrossRefGoogle ScholarPubMed
Camidge, DR, Doebele, RC and Kerr, KM (2019) Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC. Nature Reviews, Clinical Oncology 16, 341355.CrossRefGoogle ScholarPubMed
Rotow, J and Bivona, TG (2017) Understanding and targeting resistance mechanisms in NSCLC. Nature Reviews Cancer 17, 637658.CrossRefGoogle ScholarPubMed
Baluapuri, A, Wolf, E and Eilers, M (2020) Target gene-independent functions of MYC oncoproteins. Nature Reviews Molecular Cell Biology 21, 255267.CrossRefGoogle ScholarPubMed
Cuadrado, A et al. (2019) Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nature Reviews, Drug Discovery 18, 295317.CrossRefGoogle ScholarPubMed
Kotler, E et al. (2018) A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation. Molecular Cell 71, 178190. e8.CrossRefGoogle ScholarPubMed
Shaw, AT and Engelman, JA (2013) ALK In lung cancer: past, present, and future. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 31, 11051111.CrossRefGoogle ScholarPubMed
da Cunha Santos, G, Shepherd, FA and Tsao, MS (2011) EGFR Mutations and lung cancer. Annual Review of Pathology 6, 4969.CrossRefGoogle ScholarPubMed
Guertin, DA and Sabatini, DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12, 922.CrossRefGoogle ScholarPubMed
Kastenhuber, ER and Lowe, SW (2017) Putting p53 in context. Cell 170, 10621078.CrossRefGoogle ScholarPubMed
Takaoka, A et al. (2003) Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424, 516523.CrossRefGoogle ScholarPubMed
Shatz, M, Menendez, D and Resnick, MA (2012) The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells. Cancer Research 72, 39483957.CrossRefGoogle ScholarPubMed
Sun, H et al. (2020) Specific TP53 subtype as biomarker for immune checkpoint inhibitors in lung adenocarcinoma. EBioMedicine 60, 102990.CrossRefGoogle ScholarPubMed
Kato, S et al. (2017) Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clinical Cancer Research 23, 42424250.CrossRefGoogle ScholarPubMed
Cancer Genome Atlas Research, N (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543550.CrossRefGoogle Scholar
Martin Martorell, P et al. (2017) Coexistence of EGFR, KRAS, BRAF, and PIK3CA mutations and ALK rearrangement in a comprehensive cohort of 326 consecutive Spanish Nonsquamous NSCLC patients. Clinical Lung Cancer 18, e395e402.CrossRefGoogle Scholar
Roman, M et al. (2018) KRAS Oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Molecular Cancer 17, 33.CrossRefGoogle ScholarPubMed
Scheffler, M et al. (2019) K-ras mutation subtypes in NSCLC and associated co-occuring mutations in other oncogenic pathways. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 14, 606616.CrossRefGoogle ScholarPubMed
Hong, DS et al. (2020) KRAS(G12C) inhibition with Sotorasib in advanced solid tumors. New England Journal of Medicine 383, 12071217.CrossRefGoogle ScholarPubMed
Landre, T et al. (2021) Anti-PD-(L)1 for KRAS-mutant advanced non-small-cell lung cancers: a meta-analysis of randomized-controlled trials. Cancer Immunology Immunotherapy 71, 719726.CrossRefGoogle ScholarPubMed
Scheel, AH et al. (2016) PD-L1 expression in non-small cell lung cancer: correlations with genetic alterations. Oncoimmunology 5, e1131379.CrossRefGoogle ScholarPubMed
Yang, Q, Jiang, W and Hou, P (2019) Emerging role of PI3 K/AKT in tumor-related epigenetic regulation. Seminars in Cancer Biology 59, 112124.CrossRefGoogle Scholar
Fruman, DA et al. (2017) The PI3 K pathway in human disease. Cell 170, 605635.CrossRefGoogle Scholar
Alzahrani, AS (2019) PI3 K/Akt/mTOR Inhibitors in cancer: at the bench and bedside. Seminars in Cancer Biology 59, 125132.CrossRefGoogle Scholar
Vazquez, F and Devreotes, P (2006) Regulation of PTEN function as a PIP3 gatekeeper through membrane interaction. Cell Cycle 5, 15231527.CrossRefGoogle ScholarPubMed
Ahmed, SM et al. (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochimica et Biophysica Acta, Molecular Basis of Disease 1863, 585597.CrossRefGoogle ScholarPubMed
Hammad, A et al. (2019) “NRF2 addiction” in lung cancer cells and its impact on cancer therapy. Cancer Letters 467, 4049.CrossRefGoogle ScholarPubMed
Singh, A et al. (2021) NRF2 Activation promotes aggressive lung cancer and associates with poor clinical outcomes. Clinical Cancer Research 27, 877888.CrossRefGoogle ScholarPubMed
Best, SA and Sutherland, KD (2018) “Keaping” a lid on lung cancer: the Keap1-Nrf2 pathway. Cell Cycle 17, 16961707.CrossRefGoogle ScholarPubMed
Matsuoka, Y et al. (2016) IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma. British Journal of Cancer 115, 12341244.CrossRefGoogle ScholarPubMed
Shackelford, DB and Shaw, RJ (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nature Reviews Cancer 9, 563575.CrossRefGoogle ScholarPubMed
Koyama, S et al. (2016) STK11/LKB1 Deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell activity in the lung tumor microenvironment. Cancer Research 76, 9991008.CrossRefGoogle ScholarPubMed
Dong, ZY et al. (2017) EGFR Mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology 6, e1356145.CrossRefGoogle ScholarPubMed
Gainor, JF et al. (2016) 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. Clinical Cancer Research 22, 45854593.CrossRefGoogle ScholarPubMed
Dankner, M et al. (2018) Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene 37, 31833199.CrossRefGoogle ScholarPubMed
Negrao, MV et al. (2020) Molecular landscape of BRAF-mutant NSCLC reveals an association between clonality and driver mutations and identifies targetable non-V600 driver mutations. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 15, 16111623.CrossRefGoogle ScholarPubMed
Planchard, D et al. (2017) Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. The Lancet. Oncology 18, 13071316.CrossRefGoogle Scholar
Dudnik, E et al. (2018) BRAF Mutant lung cancer: programmed death ligand 1 expression, tumor mutational burden, microsatellite instability status, and response to immune check-point inhibitors. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 13, 11281137.CrossRefGoogle ScholarPubMed
Murciano-Goroff, YR et al. (2021) Immune biomarkers and response to checkpoint inhibition of BRAF(V600) and BRAF non-V600 altered lung cancers. British Journal of Cancer 126, 889898.CrossRefGoogle ScholarPubMed
Trusolino, L, Bertotti, A and Comoglio, PM (2010) MET Signalling: principles and functions in development, organ regeneration and cancer. Nature Reviews Molecular Cell Biology 11, 834848.CrossRefGoogle ScholarPubMed
Awad, MM et al. (2016) MET Exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-met overexpression. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 34, 721730.CrossRefGoogle ScholarPubMed
Li, X, Wang, R and Wang, L (2020) MET-mutant cancer and immune checkpoint inhibitors: a large database analysis. Lung Cancer 150, 256258.CrossRefGoogle ScholarPubMed
Sabari, JK et al. (2018) PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Annals of Oncology: Official Journal of the European Society for Medical Oncology 29, 20852091.CrossRefGoogle ScholarPubMed
Papaccio, F et al. (2018) HGF/MET and the immune system: relevance for cancer immunotherapy. International Journal of Molecular Sciences 19, 3595.CrossRefGoogle ScholarPubMed
Golding, B et al. (2018) The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Molecular Cancer 17, 52.CrossRefGoogle Scholar
Bakkenist, CJ and Kastan, MB (2003) DNA Damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421, 499506.CrossRefGoogle ScholarPubMed
Mitui, M et al. (2009) Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk. Human Mutation 30, 1221.CrossRefGoogle ScholarPubMed
Ali, A (2004) Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes & Development 18, 249254.CrossRefGoogle ScholarPubMed
Kumar, V, Alt, FW and Oksenych, V (2014) Functional overlaps between XLF and the ATM-dependent DNA double strand break response. DNA Repair (Amst) 16, 1122.CrossRefGoogle ScholarPubMed
Dang, CV (2012) MYC On the path to cancer. Cell 149, 2235.CrossRefGoogle ScholarPubMed
Dang, CV et al. (2006) The c-Myc target gene network. Seminars in Cancer Biology 16, 253264.CrossRefGoogle ScholarPubMed
Chen, H, Liu, H and Qing, G (2018) Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther 3, 5.CrossRefGoogle ScholarPubMed
Kortlever, RM et al. (2017) Myc cooperates with Ras by programming inflammation and immune suppression. Cell 171, 13011315. e14.CrossRefGoogle ScholarPubMed
Sanchez-Vega, F et al. (2018) Oncogenic signaling pathways in the cancer genome atlas. Cell 173, 321337. e10.CrossRefGoogle ScholarPubMed
Galan-Cobo, A et al. (2019) LKB1 And KEAP1/NRF2 pathways cooperatively promote metabolic reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma. Cancer Research 79, 32513267.CrossRefGoogle ScholarPubMed
Nissan, MH et al. (2014) Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Research 74, 23402350.CrossRefGoogle ScholarPubMed
Yuan, B et al. (2020) Co-Occurring alterations of ERBB2 exon 20 insertion in non-small cell lung cancer (NSCLC) and the potential indicator of response to Afatinib. Frontiers in Oncology 10, 729.CrossRefGoogle ScholarPubMed
Fang, W et al. (2019) Mutation variants and co-mutations as genomic modifiers of response to Afatinib inHER2-mutant lung adenocarcinoma. The Oncologist 25, e545e554.CrossRefGoogle ScholarPubMed
Mina, M et al. (2017) Conditional selection of genomic alterations dictates cancer evolution and oncogenic dependencies. Cancer Cell 32, 155168. e6.CrossRefGoogle ScholarPubMed
van de Haar, J et al. (2019) Identifying epistasis in cancer genomes: a delicate affair. Cell 177, 13751383.CrossRefGoogle ScholarPubMed
Etemadmoghadam, D et al. (2013) Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proceedings of the National Academy of Sciences of the USA 110, 1948919494.CrossRefGoogle ScholarPubMed
Brown, JS et al. (2017) Targeting DNA repair in cancer: beyond PARP inhibitors. Cancer Discovery 7, 2037.CrossRefGoogle ScholarPubMed
George, A, Kaye, S and Banerjee, S (2017) Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nature Reviews, Clinical Oncology 14, 284296.CrossRefGoogle ScholarPubMed
Carey, JPW et al. (2018) Synthetic lethality of PARP inhibitors in combination with MYC blockade is independent of BRCA Status in triple-negative breast cancer. Cancer Research 78, 742757.CrossRefGoogle ScholarPubMed
Yang, W et al. (2020) Favorable immune microenvironment in patients with EGFR and MAPK Co-mutations. Lung Cancer: Targets and Therapy 11, 5971.Google ScholarPubMed
Skoulidis, F et al. (2018) STK11/LKB1 Mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery 8, 822835.CrossRefGoogle ScholarPubMed
Peng, DH et al. (2021) Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers. Nature Communications 12, 2606.CrossRefGoogle ScholarPubMed
Arbour, KC et al. (2018) Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer. Clinical Cancer Research 24, 334340.CrossRefGoogle ScholarPubMed
Frost, N et al. (2021) KRAS(G12C)/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma. Translational Lung Cancer Research 10, 737752.CrossRefGoogle ScholarPubMed
Gao, G et al. (2020) KRAS G12D mutation predicts lower TMB and drives immune suppression in lung adenocarcinoma. Lung Cancer 149, 4145.CrossRefGoogle ScholarPubMed
Best, SA et al. (2018) Synergy between the KEAP1/NRF2 and PI3 K pathways drives non-small-cell lung cancer with an altered immune microenvironment. Cell Metabolism 27, 935943. e4.CrossRefGoogle Scholar
Jiang, T et al. (2021) Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial. Signal Transduct Target Ther 6, 355.CrossRefGoogle ScholarPubMed
Shi, Y et al. (2021) Integration of comprehensive genomic profiling, tumor mutational burden, and PD-L1 expression to identify novel biomarkers of immunotherapy in non-small cell lung cancer. Cancer Medicine 10, 22162231.CrossRefGoogle ScholarPubMed
Chen, Y et al. (2019) Association of tumor protein p53 and ataxia-telangiectasia mutated comutation with response to immune checkpoint inhibitors and mortality in patients with non-small cell lung cancer. JAMA Netw Open 2, e1911895.CrossRefGoogle ScholarPubMed
Mazzotta, M et al. (2020) Efficacy of immunotherapy in lung cancer with co-occurring mutations in NOTCH and homologous repair genes. Journal for Immunotherapy of Cancer 8, e000946.CrossRefGoogle ScholarPubMed
Scarbrough, PM et al. (2016) A cross-cancer genetic association analysis of the DNA repair and DNA damage signaling pathways for lung, ovary, prostate, breast, and colorectal cancer. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 25, 193200.CrossRefGoogle ScholarPubMed
Chang, A et al. (2021) Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer. Cancer Research 81, 33583373.CrossRefGoogle ScholarPubMed
Zhang, P and Huang, Y (2021) Genomic alterations in KMT2 family predict outcome of immune checkpoint therapy in multiple cancers. Journal of Hematology & Oncology 14, 39.CrossRefGoogle ScholarPubMed
Wong, SK et al. (2021) MET Exon 14 skipping mutation positive non-small cell lung cancer: response to systemic therapy. Lung Cancer 154, 142145.CrossRefGoogle ScholarPubMed
Albitar, M et al. (2018) Correlation of MET gene amplification and TP53 mutation with PD-L1 expression in non-small cell lung cancer. Oncotarget 9, 1368213693.CrossRefGoogle ScholarPubMed
Labbe, C et al. (2017) Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Lung Cancer 111, 2329.CrossRefGoogle Scholar
Zheng, C et al. (2020) Coexisting EGFR and TP53 mutations in lung adenocarcinoma patients are associated with COMP and ITGB8 upregulation and poor prognosis. Frontiers in Molecular Biosciences 7, 30.CrossRefGoogle ScholarPubMed
Zhao, Y et al. (2020) EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis. Journal of Cancer Research and Clinical Oncology 146, 17811789.CrossRefGoogle ScholarPubMed
Gu, M, Xu, T and Chang, P (2021) KRAS/LKB1 and KRAS/TP53 co-mutations create divergent immune signatures in lung adenocarcinomas. Therapeutic Advances in Medical Oncology 13, 17588359211006950.CrossRefGoogle ScholarPubMed
Wang, L et al. (2014) PIK3CA Mutations frequently coexist with EGFR/KRAS mutations in non-small cell lung cancer and suggest poor prognosis in EGFR/KRAS wildtype subgroup. PLoS ONE 9, e88291.CrossRefGoogle ScholarPubMed
Lee, CK et al. (2017) Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer-A meta-analysis. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 12, 403407.CrossRefGoogle ScholarPubMed
Cho, JW et al. (2021) Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer. Nature Communications 12, 6068.CrossRefGoogle ScholarPubMed
Chen, N et al. (2017) KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma. Cancer Immunology Immunotherapy 66, 11751187.CrossRefGoogle ScholarPubMed
Shamalov, K et al. (2017) The mutational status of p53 can influence its recognition by human T-cells. Oncoimmunology 6, e1285990.CrossRefGoogle ScholarPubMed
Topper, MJ et al. (2017) Epigenetic therapy ties MYC depletion to reversing immune evasion and treating lung cancer. Cell 171, 12841300. e21.CrossRefGoogle ScholarPubMed
Parkes, EE et al. (2017) Activation of STING-dependent innate immune signaling by S-phase-specific DNA damage in breast cancer. Journal of the National Cancer Institute 109, djw199.CrossRefGoogle ScholarPubMed
Thiem, A et al. (2019) IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression. Journal of Experimental & Clinical Cancer Research: CR 38, 397.CrossRefGoogle ScholarPubMed
Lei, TY et al. (2021) The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke. Journal of Neuroinflammation 18, 25.CrossRefGoogle ScholarPubMed
Nogami, N et al. (2021) IMPower150 final exploratory analyses for Atezolizumab Plus bevacizumab and chemotherapy in key NSCLC patient subgroups with EGFR mutations or metastases in the liver or brain. Journal of Thoracic Oncology 17, 309323.CrossRefGoogle ScholarPubMed
Peng, S et al. (2019) EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression. Molecular Cancer 18, 165.CrossRefGoogle ScholarPubMed
Matsuzaki, S et al. (2010) Lysophosphatidic acid inhibits CC chemokine ligand 5/RANTES production by blocking IRF-1-mediated gene transcription in human bronchial epithelial cells. Journal of Immunology 185, 48634872.CrossRefGoogle ScholarPubMed
Coelho, MA et al. (2017) Oncogenic RAS signaling promotes tumor immunoresistance by stabilizing PD-L1 mRNA. Immunity 47, 10831099. e6.CrossRefGoogle ScholarPubMed
Barber, GN (2015) STING: infection, inflammation and cancer. Nature Reviews Immunology 15, 760770.CrossRefGoogle Scholar
Hartlova, A et al. (2015) DNA Damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity 42, 332343.CrossRefGoogle ScholarPubMed
Zhang, Y et al. (2021) MET Amplification attenuates LungTumor response to immunotherapy by inhibiting STING. Cancer Discovery 11, 27262737.CrossRefGoogle Scholar
Schabath, MB et al. (2016) Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene 35, 32093216.CrossRefGoogle ScholarPubMed
Kitajima, S et al. (2019) Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer. Cancer Discovery 9, 3445.CrossRefGoogle ScholarPubMed
Schumacher, TN and Schreiber, RD (2015) Neoantigens in cancer immunotherapy. Science 348, 6974.CrossRefGoogle ScholarPubMed
Zhao, L et al. (2020) TP53 Somatic mutations are associated with poor survival in non-small cell lung cancer patients who undergo immunotherapy. Aging (Albany NY) 12, 1455614568.CrossRefGoogle ScholarPubMed
Cha, YJ et al. (2016) Clinicopathological and prognostic significance of programmed cell death ligand-1 expression in lung adenocarcinoma and its relationship with p53 status. Lung Cancer 97, 7380.CrossRefGoogle ScholarPubMed
Cortez, MA et al. (2016) PDL1 Regulation by p53 via miR-34. Journal of the National Cancer Institute 108, djv303.CrossRefGoogle ScholarPubMed
Singal, G et al. (2019) Association of patient characteristics and tumor genomics with clinical outcomes among patients with non-small cell lung cancer using a clinicogenomic database. JAMA 321, 13911399.CrossRefGoogle ScholarPubMed
Gettinger, S and Politi, K (2016) PD-1 Axis inhibitors in EGFR- and ALK-driven lung cancer: lost cause? Clinical Cancer Research: an Official Journal of the American Association for Cancer Research 22, 45394541.CrossRefGoogle ScholarPubMed
Dong, ZY et al. (2017) Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clinical Cancer Research 23, 30123024.CrossRefGoogle ScholarPubMed
Wohlhieter, CA et al. (2020) Concurrent mutations in STK11 and KEAP1 promote ferroptosis protection and SCD1 dependence in lung cancer. Cell Reports 33, 108444.CrossRefGoogle ScholarPubMed
Liu, YT and Sun, ZJ (2021) Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics 11, 53655386.CrossRefGoogle ScholarPubMed
Galon, J and Bruni, D (2019) Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nature Reviews, Drug Discovery 18, 197218.CrossRefGoogle ScholarPubMed
Hyman, DM, Taylor, BS and Baselga, J (2017) Implementing genome-driven oncology. Cell 168, 584599.CrossRefGoogle ScholarPubMed

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Cancer mutation profiles predict ICIs efficacy in patients with non-small cell lung cancer
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Cancer mutation profiles predict ICIs efficacy in patients with non-small cell lung cancer
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Cancer mutation profiles predict ICIs efficacy in patients with non-small cell lung cancer
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *