Abstract
BackgroundClinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in EGFR-mutation patients is unknown.MethodsThe mRNA expression and mutation data and lung adenocarcinoma (LUAD) clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Profiles describing the immune landscape of patients with EGFR mutations were characterized by differences in tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).ResultsIn total, the TCGA data for 585 patients were analyzed. Among these patients, 98 had EGFR mutations. The TMB was lower in the EGFR group (3.94 mut/Mb) than in the KRAS mutation group (6.09 mut/Mb, P < 0.001) and the entire LUAD (6.58 mut/Mb, P < 0.001). The EGFR group had a lower population of activated immune cells and an even higher score of immunosuppressive cells. A further inter-group comparison showed that differences in the TMB and tumor-infiltrating lymphocytes were only found between patients with oncogenic mutations and unknown mutation. Meanwhile, there were more myeloid dendritic cells (DCs) in EGFR 19del than in L858R-mutation patients and in common mutation patents than in uncommon mutation patients (P < 0.05). Additionally, we established a D score, where D = MCP-counter score for cytotoxic T lymphocytes (CTLs)/MCP-counter score for myeloid DCs. Further analysis revealed that lower D scores indicated immune suppression and were negatively related to several immunotherapy biomarkers.ConclusionsThe TIME of EGFR mutant NSCLC was immunosuppressive. Myeloid DCs gradually increased in EGFR 19del, L858R, and uncommon mutations. The potential role of CTLs and DCs in the TIME of patients requires further investigation.
Highlights
Lung cancer is one of the leading causes of cancer mortality worldwide [1]
The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) mRNA expression data, mutation data, and clinical information were downloaded from TCGA and the University of California at Santa Cruz Xena (UCSC Xena; http://xena.ucsc.edu/)
The patients were divided into four groups according to their EGFRmutation type (19del, L858R, uncommon mutation, unknown mutation group)
Summary
Lung cancer is one of the leading causes of cancer mortality worldwide [1]. 85% of patients with lung cancer are diagnosed with non-small-cell lung cancer (NSCLC). The two main histological subtypes of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ADC and SCC show different characteristic according to the mutation landscape at the molecular level. The epidermal growth factor receptor (EGFR) mutation is one of the most common mutated genes detected in adenocarcinoma. Other mutations located in exons 18 and 20 are rare but can cause EGFR gene activation [2]. Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can benefit from immunotherapy. The TIME transformational process in EGFR-mutation patients is unknown
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