Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations

Wang Yang, Naifei Chen, Lingyu Li, Xiao Chen, Xiangliang Liu, Yongfei Zhang, Jiuwei Cui The Cancer Center of the First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Jiuwei Cui Tel +86 431-8878-2178Fax +86-0431-88786134Email cuijw@jlu.edu.c...

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Autores principales:	Yang W, Chen N, Li L, Chen X, Liu X, Zhang Y, Cui J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	epidermal growth factor receptor (egfr) mutation tumor mutation burden (tmb) immune checkpoint inhibitor (ici) lung adenocarcinoma (luad). Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4a6b99e8049947aca2306b8e593e3bcc
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spelling	oai:doaj.org-article:4a6b99e8049947aca2306b8e593e3bcc2021-12-02T10:15:44ZFavorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations1179-2728https://doaj.org/article/4a6b99e8049947aca2306b8e593e3bcc2020-09-01T00:00:00Zhttps://www.dovepress.com/favorable-immune-microenvironment-in-patients-with-egfr-and-mapk-co-mu-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Wang Yang, Naifei Chen, Lingyu Li, Xiao Chen, Xiangliang Liu, Yongfei Zhang, Jiuwei Cui The Cancer Center of the First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Jiuwei Cui Tel +86 431-8878-2178Fax +86-0431-88786134Email cuijw@jlu.edu.cnPurpose: Although EGFR-mutated patients generally do not benefit from checkpoint inhibitors (ICIs), some patients in the KEYNOTE-001 study consistently benefited from this treatment. This study investigated immune microenvironment characteristics to identify the subgroup of patients that may benefit from ICIs.Materials and Methods: Using data from The Cancer Genome Atlas Program (TCGA) and Cancer Proteome Atlas, TMB and protein level of PD-L1 were explored in the patients with EGFR mutations and wild-type patients. Different patterns of EGFR mutations (according to EGFR co-mutation with different downstream pathway genesets) were used to group EGFR mutation population. Estimated infiltration analyses were used to explore changes in the immune microenvironment.Results: This study analyzed somatic mutation data from 1287 patients from five cohorts (TCGA, Broad, The Tumour Sequencing Project, Memorial Sloan Kettering Cancer Center, Catalogue Of Somatic Mutations In Cancer database). The probability of EGFR mutation was approximately 14.30% (184/1287) and the co-mutation rate was 11.41% (21/184) in patients with EGFR mutations. Glycosaminoglycan-related pathways were significantly upregulated in the EGFR mutant group. EGFR-mutated patients had lower TMB and PD-L1 protein levels than those in wild-type patients. Increase immature DCs infiltration and decreased NK CD56dim, T gamma delta, cytotoxic, and Th2 cell infiltration were the main immune changes in EGFR-mutated patients. Patients with EGFR-MAPK co-mutations had higher levels of TMB and PD-L1 protein expression. Meanwhile, the co-mutated patients had a similar immune microenvironment as that in wild-type patients.Conclusion: In this study, we defined a subgroup of patients with EGFR-MAPK co-mutations. These co-mutated patients may benefit from ICI treatment.Keywords: epidermal growth factor receptor, EGFR mutation, tumor mutation burden, TMB, immune checkpoint inhibitor, ICI, lung adenocarcinoma, LUADYang WChen NLi LChen XLiu XZhang YCui JDove Medical Pressarticleepidermal growth factor receptor (egfr) mutationtumor mutation burden (tmb)immune checkpoint inhibitor (ici)lung adenocarcinoma (luad).Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 11, Pp 59-71 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	epidermal growth factor receptor (egfr) mutation tumor mutation burden (tmb) immune checkpoint inhibitor (ici) lung adenocarcinoma (luad). Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	epidermal growth factor receptor (egfr) mutation tumor mutation burden (tmb) immune checkpoint inhibitor (ici) lung adenocarcinoma (luad). Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yang W Chen N Li L Chen X Liu X Zhang Y Cui J Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
description	Wang Yang, Naifei Chen, Lingyu Li, Xiao Chen, Xiangliang Liu, Yongfei Zhang, Jiuwei Cui The Cancer Center of the First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Jiuwei Cui Tel +86 431-8878-2178Fax +86-0431-88786134Email cuijw@jlu.edu.cnPurpose: Although EGFR-mutated patients generally do not benefit from checkpoint inhibitors (ICIs), some patients in the KEYNOTE-001 study consistently benefited from this treatment. This study investigated immune microenvironment characteristics to identify the subgroup of patients that may benefit from ICIs.Materials and Methods: Using data from The Cancer Genome Atlas Program (TCGA) and Cancer Proteome Atlas, TMB and protein level of PD-L1 were explored in the patients with EGFR mutations and wild-type patients. Different patterns of EGFR mutations (according to EGFR co-mutation with different downstream pathway genesets) were used to group EGFR mutation population. Estimated infiltration analyses were used to explore changes in the immune microenvironment.Results: This study analyzed somatic mutation data from 1287 patients from five cohorts (TCGA, Broad, The Tumour Sequencing Project, Memorial Sloan Kettering Cancer Center, Catalogue Of Somatic Mutations In Cancer database). The probability of EGFR mutation was approximately 14.30% (184/1287) and the co-mutation rate was 11.41% (21/184) in patients with EGFR mutations. Glycosaminoglycan-related pathways were significantly upregulated in the EGFR mutant group. EGFR-mutated patients had lower TMB and PD-L1 protein levels than those in wild-type patients. Increase immature DCs infiltration and decreased NK CD56dim, T gamma delta, cytotoxic, and Th2 cell infiltration were the main immune changes in EGFR-mutated patients. Patients with EGFR-MAPK co-mutations had higher levels of TMB and PD-L1 protein expression. Meanwhile, the co-mutated patients had a similar immune microenvironment as that in wild-type patients.Conclusion: In this study, we defined a subgroup of patients with EGFR-MAPK co-mutations. These co-mutated patients may benefit from ICI treatment.Keywords: epidermal growth factor receptor, EGFR mutation, tumor mutation burden, TMB, immune checkpoint inhibitor, ICI, lung adenocarcinoma, LUAD
format	article
author	Yang W Chen N Li L Chen X Liu X Zhang Y Cui J
author_facet	Yang W Chen N Li L Chen X Liu X Zhang Y Cui J
author_sort	Yang W
title	Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
title_short	Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
title_full	Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
title_fullStr	Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
title_full_unstemmed	Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations
title_sort	favorable immune microenvironment in patients with egfr and mapk co-mutations
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4a6b99e8049947aca2306b8e593e3bcc
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Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations

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