Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma

• DOI: 10.1136/jitc-2021-003534
• Publication Date: 2022-02-09T16:33:10Z
• Authors: Lei Yang; Yun-Ting He; Song Dong; Xue-Wu Wei; Zhi-Hong Chen; Bo Zhang; Wei-Dong Chen; Xiao-Rong Yang; Fen Wang; Xue-Meng Shang; Wen-Zhao Zhong; Yi-Long Wu; Qing Zhou
• Keywords: Immune checkpoint

Backgrounds Immunotherapy is less effective in patients with epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC). Lower programmed cell death-ligand 1 (PD-L1) expression and tumor mutation burden (TMB) are reported to be the underlying mechanism. Being another important affect efficacy of immunotherapy, microenvironment (TME) characteristics this subgroup NSCLC not comprehensively understood up date. Hence, we initiated study describe specific TME EGFR-mutant adenocarcinoma (LUAD) from cellular compositional functional perspectives better understand immune landscape most common subtype NSCLC. Methods We used single-cell transcriptome sequencing multiplex immunohistochemistry investigate EGFR wild-type LUADs determined immunotherapy. analyzed single cells nine treatment-naïve samples compared them three post-immunotherapy previously perspective using bioinformatics methods. Results found that malignant epithelial had similar non-responders. LUAD lacked CD8 + tissue-resident memory (TRM) cells, which could promote tertiary lymphoid structure generation by secreting CXCL13. In addition, other types, including tumor-associated macrophages cancer-associated fibroblasts, capable recruiting, retaining, expanding TRM TME, were also deficient LUAD. Furthermore, significantly crosstalk between T types via death-1 (PD-1) PD-L1 or checkpoints Conclusions Our findings provide a comprehensive understanding at level. Based on results, many components might have negative impact through influencing TRM. Lack key responsible for suppressive