Immunomodulatory role of oncogenic alterations in non-small cell lung cancer: a review of implications for immunotherapy

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

Campos-Parra, A. D., Aviles, A., Contreras-Reyes, S., Rojas-Marin, C. E., Sanchez-Reyes, R., Borbolla-Escoboza, R. J., & Arrieta, O. (2014). Relevance of the novel IASLC/ATS/ERS classification of lung adenocarcinoma in advanced disease. European Respiratory Journal, 43(5), 1439–1447. https://doi.org/10.1183/09031936.00138813

Article  PubMed  Google Scholar 

Chevallier, M., Borgeaud, M., Addeo, A., & Friedlaender, A. (2021). Oncogenic driver mutations in non-small cell lung cancer: Past, present and future. World Journal of Clinical Oncology, 12(4), 217–237. https://doi.org/10.5306/wjco.v12.i4.217

Article  PubMed  PubMed Central  Google Scholar 

Reungwetwattana, T., Weroha, S. J., & Molina, J. R. (2012). Oncogenic Pathways, Molecularly Targeted Therapies, and Highlighted Clinical Trials in Non–Small-Cell Lung Cancer (NSCLC). Clinical Lung Cancer, 13(4), 252–266. https://doi.org/10.1016/j.cllc.2011.09.004

Article  CAS  PubMed  Google Scholar 

Dolly, S. O., Collins, D. C., Sundar, R., Popat, S., & Yap, T. A. (2017). Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer. Drugs, 77(8), 813–827. https://doi.org/10.1007/s40265-017-0732-2

Article  CAS  PubMed  Google Scholar 

Barrón, F., Cardona, A. F., Corrales, L., Ramirez-Tirado, L.-A., Caballe-Perez, E., Sanchez, G., … Arrieta, O. (2018). Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation. Journal of Thoracic Disease, 10(4), 2166–2178. https://doi.org/10.21037/jtd.2018.03.106

Burdett, N., & Desai, J. (2020). New biomarkers for checkpoint inhibitor therapy. ESMO Open, 5, e000597. https://doi.org/10.1136/esmoopen-2019-000597

Article  PubMed  PubMed Central  Google Scholar 

Passaro, A., Attili, I., Morganti, S., Del Signore, E., Gianoncelli, L., Spitaleri, G., … de Marinis, F. (2020). Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: A critical review of published data. Cancer Treatment Reviews, 89, 102085. https://doi.org/10.1016/j.ctrv.2020.102085

Herbst, R. S., Giaccone, G., de Marinis, F., Reinmuth, N., Vergnenegre, A., Barrios, C. H., … Spigel, D. R. (2020). Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. New England Journal of Medicine, 383(14), 1328–1339. https://doi.org/10.1056/NEJMoa1917346

Mok, T. S. K., Wu, Y.-L., Kudaba, I., Kowalski, D. M., Cho, B. C., Turna, H. Z., … Zippelius, A. (2019). Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. The Lancet, 393(10183), 1819–1830. https://doi.org/10.1016/S0140-6736(18)32409-7

Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., … Brahmer, J. R. (2016). Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823–1833. https://doi.org/10.1056/NEJMoa1606774

Dudnik, E., Bshara, E., Grubstein, A., Fridel, L., Shochat, T., Roisman, L. C., … Peled, N. (2018). Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi). Lung Cancer, 124, 117–124. https://doi.org/10.1016/j.lungcan.2018.07.044

Mazieres, J., Drilon, A., Lusque, A., Mhanna, L., Cortot, A. B., Mezquita, L., … Gautschi, O. (2019). Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: Results from the IMMUNOTARGET registry. Annals of Oncology, 30(8), 1321–1328. https://doi.org/10.1093/annonc/mdz167

Herbst, R. S., de Marinis, F., Giaccone, G., Reinmuth, N., Vergnenegre, A., Barrios, C. H., … Jassem, J. (2019). Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in KEYNOTE-042. Annals of Oncology, 30, xi62–xi63. https://doi.org/10.1093/annonc/mdz453

Dudnik, E., Peled, N., Nechushtan, H., Wollner, M., Onn, A., Agbarya, A., … Bar, J. (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, 13(8), 1128–1137. https://doi.org/10.1016/j.jtho.2018.04.024

Lee, C. K., Man, J., Lord, S., Links, M., Gebski, V., Mok, T., & Yang, J. C. H. (2017). Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer—A Meta-Analysis. Journal of Thoracic Oncology, 12(2), 403–407. https://doi.org/10.1016/j.jtho.2016.10.007

Article  PubMed  Google Scholar 

Li, L., Li, M., & Wang, X. (2020). Cancer type-dependent correlations between TP53 mutations and antitumor immunity. DNA Repair, 88. https://doi.org/10.1016/j.dnarep.2020.102785

Kron, A., Scheffler, M., Heydt, C., Ruge, L., Schaepers, C., Eisert, A. K., … Wolf, J. (2021). Genetic Heterogeneity of MET-Aberrant NSCLC and Its Impact on the Outcome of Immunotherapy. Journal of Thoracic Oncology, 16(4), 572–582. https://doi.org/10.1016/j.jtho.2020.11.017

Jin, Y., Xue, Q., Shen, X., Zheng, Q., Chen, H., Zhou, X., & Li, Y. (2022). PD-L1 Expression and Comprehensive Molecular Profiling Predict Survival in Nonsmall Cell Lung Cancer: A Real-World Study of a Large Chinese Cohort. Clinical Lung Cancer, 23(1), 43–51. https://doi.org/10.1016/j.cllc.2021.08.009

Article  CAS  PubMed  Google Scholar 

Yamada, T., Hirai, S., Katayama, Y., Yoshimura, A., Shiotsu, S., Watanabe, S., … Takayama, K. (2019). Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer. Cancer Medicine, 8(4), 1521–1529. https://doi.org/10.1002/cam4.2037

S. Gadgeel, Rodriguez-Abreu, E., Felip, E., Esteban, G., Speranza, M., Reck, R., … Ayers, B. (2019). KRAS mutational status and efficacy in KEYNOTE-189: Pembrolizumab(pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC. Annals of Oncology, 30, xi62–xi63. https://doi.org/10.1093/annonc/mdz453

Wang, L., Ren, Z., Yu, B., & Tang, J. (2021). Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors. Journal of Translational Medicine, 19(1). https://doi.org/10.1186/s12967-020-02679-0

Brea, E. J., Oh, C. Y., Manchado, E., Budhu, S., Gejman, R. S., Mo, G., … Scheinberg, D. A. (2016). Kinase regulation of human MHC class i molecule expression on cancer cells. Cancer Immunology Research, 4(11), 936–947. https://doi.org/10.1158/2326-6066.CIR-16-0177

Della Corte, C. M., Sen, T., Gay, C. M., Ramkumar, K., Diao, L., Cardnell, R. J., … Byers, L. A. (2020). STING Pathway Expression Identifies NSCLC With an Immune-Responsive Phenotype. Journal of Thoracic Oncology, 15(5), 777–791. https://doi.org/10.1016/j.jtho.2020.01.009

Shajani-Yi, Z., de Abreu, F. B., Peterson, J. D., & Tsongalis, G. J. (2018). Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non-Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing. Neoplasia (United States), 20(3), 256–262. https://doi.org/10.1016/j.neo.2017.12.005

Article  CAS  Google Scholar 

Hernández-Pedro, N., Soca-Chafre, G., Alaez-Versón, C., Carrillo-Sánchez, K., Avilés-Salas, A., Vergara, E., & Arrieta, O. (2019). Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population. Salud Pública de México, 61(3, may-jun), 308. https://doi.org/10.21149/10113

Oduah, E. I., & Grossman, S. R. (2020, April 2). Harnessing the vulnerabilities of p53 mutants in lung cancer–Focusing on the proteasome: a new trick for an old foe? Cancer Biology and Therapy. Taylor and Francis Inc. https://doi.org/10.1080/15384047.2019.1702403

Hao, F., Gu, L., & Zhong, D. (2022). TP53 Mutation Mapping in Advanced Non-Small Cell Lung Cancer: A Real-World Retrospective Cohort Study. Current Oncology, 2022, 7411–7419. https://doi.org/10.3390/curroncol29100582

Article  Google Scholar 

Dong, Z.-Y., Zhong, W.-Z., Zhang, X.-C., Su, J., Xie, Z., Liu, S.-Y., … Wu, Y.-L. (2017). Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma. Clinical Cancer Research, 23(12), 3012–3024. https://doi.org/10.1158/1078-0432.CCR-16-2554

Cha, Y. J., Kim, H. R., Lee, C. Y., Cho, B. C., & Shim, H. S. (2016). Clinicopathological and prognostic significance of programmed cell death ligand-1 expression in lung adenocarcinoma and its relationship with p53 status. Lung Cancer, 97, 73–80. https://doi.org/10.1016/j.lungcan.2016.05.001

Article  PubMed  Google Scholar 

Liu, Y., Wu, A., Li, X., Wang, S., Fang, S., & Mo, Y. (2022). A retrospective analysis of eleven gene mutations, PD-L1 expression and clinicopathological characteristics in non-small cell lung cancer patients. Asian Journal of Surgery, 45(1), 367–375. https://doi.org/10.1016/j.asjsur.2021.06.030

Article  PubMed  Google Scholar 

Sun, H., Liu, S. Y., Zhou, J. Y., Xu, J. T., Zhang, H. K., Yan, H. H., … Wu, Y. L. (2020). Specific TP53 subtype as biomarker for immune checkpoint inhibitors in lung adenocarcinoma. EBioMedicine, 60. https://doi.org/10.1016/j.ebiom.2020.102990

Zhang, N., Wu, J., Yu, J., Zhu, H., Yang, M., & Li, R. (2020). Integrating Imaging, Histologic, and Genetic Features to Predict Tumor Mutation Burden of Non–Small-Cell Lung Cancer. Clinical Lung Cancer, 21(3), e151–e163. https://doi.org/10.1016/j.cllc.2019.10.016

Article  CAS  PubMed  Google Scholar 

Lin, X., Wang, L., Xie, X., Qin, Y., Xie, Z., Ouyang, M., & Zhou, C. (2020). Prognostic Biomarker TP53 Mutations for Immune Checkpoint Blockade Therapy and Its Association With Tumor Microenvironment of Lung Adenocarcinoma. Frontiers in Molecular Biosciences, 7. https://doi.org/10.3389/fmolb.2020.602328

Chen, Y., Chen, G., Li, J., Huang, Y. Y., Li, Y., Lin, J., … Pan, J. J. (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 network open, 2(9), e1911895. https://doi.org/10.1001/jamanetworkopen.2019.11895

Assoun, S., Theou-Anton, N., Nguenang, M., Cazes, A., Danel, C., Abbar, B., … Khalil, A. (2021). Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer, 132, 65–71. https://doi.org/10.1016/j.lungcan.2019.04.005ï

Salgia, R., Pharaon, R., Mambetsariev, I., Nam, A., & Sattler, M. (2021, January 19). The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Cell Reports Medicine. Cell Press. https://doi.org/10.1016/j.xcrm.2020.100186

Thein, K. Z., Biter, A. B., & Hong, D. S. (2020). Therapeutics Targeting Mutant KRAS. https://doi.org/10.1146/annurev-med-080819

Article  Google Scholar 

Ferrer, I., Zugazagoitia, J., Herbertz, S., John, W., Paz-Ares, L., & Schmid-Bindert, G. (2018). KRAS-Mutant non-small cell lung cancer: From biology to therapy. Lung Cancer, 124(July), 53–64. https://doi.org/10.1016/j.lungcan.2018.07.013

Article  PubMed  Google Scholar 

Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., … Lipford, J. R. (2019). The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature, 575(7781), 217–223. https://doi.org/10.1038/s41586-019-1694-1

Jeanson, A., Tomasini, P., Souquet-Bressand, M., Brandone, N., Boucekine, M., Grangeon, M., … Mascaux, C. (2019). Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC). Journal of Thoracic Oncology, 14(6), 1095–1101. https://doi.org/10.1016/j.jtho.2019.01.011

Ebert, P. J. R., Cheung, J., Yang, Y., McNamara, E., Hong, R., Moskalenko, M., … Mellman, I. (2016). MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade. Immunity, 44(3), 609–621. https://doi.org/10.1016/j.immuni.2016.01.024

Briere, D., Calinisan, A., Aranda, R., Sukhadar, N., Hargis, L., Gatto, S., … Olson, P. (2019). The KRASG12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Abstract LB-C09. https://doi.org/10.1158/1535-7163.mct-20-0462

Coelho, M. A., de Carné Trécesson, S., Rana, S., Zecchin, D., Moore, C., Molina-Arcas, M., … Downward, J. (2017). Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. Immunity, 47(6), 1083–1099.e6. https://doi.org/10.1016/j.immuni.2017.11.016

Gao, G., Liao, W., Ma, Q., Zhang, B., Chen, Y., & Wang, Y. (2020). KRAS G12D mutation predicts lower TMB and drives immune suppression in lung adenocarcinoma. Lung Cancer, 149(September), 41–45. https://doi.org/10.1016/j.lungcan.2020.09.004

Article  PubMed  Google Scholar 

Chen, H., & Zhao, J. (2020). KRAS oncogene may be another target conquered in non-small cell lung cancer (NSCLC). Thoracic Cancer, 11(12), 3425–3435. https://doi.org/10.1111/1759-7714.13538

Article  PubMed  PubMed Central  Google Scholar 

Han Kim, J., Su Kim, H., & Jun Kim, B. (2017). Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review. Oncotarget (Vol. 8). https://doi.org/10.18632/oncotarget.17594

Rittmeyer, A., Barlesi, F., Waterkamp, D., Park, K., Ciardiello, F., von Pawel, J., … Gandara, D. R. (2017). Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. The Lancet, 389(10066), 255–265. https://doi.org/10.1016/S0140-6736(16)32517-X

Ricciuti, B., Arbour, K. C., Lin, J. J., Vajdi, A., Vokes, N., Hong, L., … Awad, M. M. (2022). Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status. Journal of Thoracic Oncology, 17(3), 399–410. https://doi.org/10.1016/j.jtho.2021.10.013

Pavan, A., Bragadin, A. B., Calvetti, L., Ferro, A., Zulato, E., Attili, I., … Bonanno, L. (2021). Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: Impact of STK11, KRAS and TP53 mutations and co-mutations on outcome. Translational Lung Cancer Research, 10(1), 202–220. https://doi.org/10.21037/tlcr-20-674

Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., … Heymach, J. V. (2018). STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 8(7), 822–835. https://doi.org/10.1158/2159-8290.CD-18-0099

Kitajima, S., Ivanova, E., Guo, S., Yoshida, R., Campisi, M., Sundararaman, S. K., … Barbie, D. A. (2019). Suppression of STING associated with lkb1 loss in KRAS-driven lung cancer. Cancer Discovery, 9(1), 34–45. https://doi.org/10.1158/2159-8290.CD-18-0689

Liu, C., Zheng, S., Jin, R., Wang, X., Wang, F., Zang, R., … He, J. (2020). The superior efficacy of anti-PD-1/PD-L1 immunotherapy in KRAS-mutant non-small cell lung cancer that correlates with an inflammatory phenotype and increased immunogenicity. Cancer Letters, 470, 95–105. https://doi.org/10.1016/j.canlet.2019.10.027

van Maldegem, F., & Downward, J. (2020). Mutant KRAS at the Heart of Tumor Immune Evasion. Immunity, 52(1), 14–16. https://doi.org/10.1016/j.immuni.2019.12.013

Article  CAS  PubMed  Google Scholar 

Werutsky, G., Debiasi, M., Sampaio, F. H., Nunes Filho, P. R., Mathias, C., Zukin, M., … Lopes, G. (2016). P1.08: Updated Analysis of Global Epidemiology of EGFR Mutation in Advanced Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 11(10), S184–S185.

Comments (0)

No login
gif