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Lung adenocarcinoma patients with KEAP1 mutation harboring low immune cell infiltration and low activity of immune environment

Authors :
Wanwan Cheng
Bin Xu
Haitao Zhang
Shencun Fang
Source :
Thoracic Cancer, Vol 12, Iss 18, Pp 2458-2467 (2021)
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

Abstract Background Kelch‐like ECH‐associated protein 1 (KEAP1) has been identified as a cancer driver gene in lung adenocarcinoma (LUAD), and increased evidence has given us clues about the association of KEAP1 mutation and immune characteristics. We assessed the association between KEAP1 mutation and tumor microenvironment in LUAD systematically. Methods With the data collected from The Cancer Genome Atlas (TCGA), we evaluated the association of KEAP1 mutation with tumor infiltrating leukocytes (TILs), including dendritic cell, CD8 T cell, CD4 T cell, neutrophil, B cells, and macrophage. Expression differences of the markers of those immune cells were also measured. We further compared the expression of antigen presentation genes and chemokines and the enrichment score of immune‐related pathways. Results KEAP1 mutation had significant association with lower TILs and cytotoxic T lymphocyte. Strikingly, almost all of antigen presentation genes and chemokine showed lower expression in KEAP1‐mutated tumors. Moreover, most of immune‐related pathways were less active in KEAP1‐mutated tumors. As expected, KEAP1‐wild type LUADs favored better overall survival after immunotherapy. Finally, one patient harboring KEAP1 mutation along with a lack of immune cells infiltration in tumor microenvironment failed to respond to checkpoint inhibitor despite high tumor mutational burden (TMB). Conclusions KEAP1 mutation has a significant effect on the tumor immune milieu of LUAD and may play as a predictive biomarker of immunotherapy for LUAD patients.

Details

Language :
English
ISSN :
17597714 and 17597706
Volume :
12
Issue :
18
Database :
Directory of Open Access Journals
Journal :
Thoracic Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.93c5c5846d83423cb26f36cbfd7d9edf
Document Type :
article
Full Text :
https://doi.org/10.1111/1759-7714.14089