AUTHOR=Li Teng , Pang Xiaocong , Wang Junyun , Wang Shouzheng , Guo Yiying , He Ning , Xing Puyuan , Li Junling 

TITLE=Exploration of the Tumor-Suppressive Immune Microenvironment by Integrated Analysis in EGFR-Mutant Lung Adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.591922

DOI=10.3389/fonc.2021.591922

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (<italic>EGFR</italic>) 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 <italic>EGFR</italic>-mutation patients is unknown.</p></sec><sec><title>Methods</title><p>The 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 <italic>EGFR</italic> mutations were characterized by differences in tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).</p></sec><sec><title>Results</title><p>In total, the TCGA data for 585 patients were analyzed. Among these patients, 98 had <italic>EGFR</italic> mutations. The TMB was lower in the <italic>EGFR</italic> group (3.94 mut/Mb) than in the <italic>KRAS</italic> mutation group (6.09 mut/Mb, <italic>P</italic> &lt; 0.001) and the entire LUAD (6.58 mut/Mb, <italic>P</italic> &lt; 0.001). The <italic>EGFR</italic> 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 <italic>EGFR</italic> 19del than in L858R-mutation patients and in common mutation patents than in uncommon mutation patients (<italic>P</italic> &lt; 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.</p></sec><sec><title>Conclusions</title><p>The TIME of <italic>EGFR</italic> mutant NSCLC was immunosuppressive. Myeloid DCs gradually increased in <italic>EGFR</italic> 19del, L858R, and uncommon mutations. The potential role of CTLs and DCs in the TIME of patients requires further investigation.</p></sec>