Single-cell transcriptome reveals drug-resistance signature and immunosuppressive microenvironment in lung adenocarcinoma harboring EGFR mutation

A majority of EGFR-mutated lung adenocarcinoma (LUAD) inevitably develops acquired resistance to tyrosine kinase inhibitor (TKI) therapy within 2 years. Due to the heterogeneous tumor microenvironment (TME) and discrepant immunotherapy responses in patients with different EGFR mutation statuses, it is necessary to characterize the immune signatures during tumor resistance, facilitating the explorations of resistance mechanisms and drug discoveries. Overall design: Six advanced LUAD patients harboring EGFR mutations were enrolled in this study, and tumor tissues were collected from 3 initially diagnosed (ID group) and 3 EGFR-TKIs resistant (Resistance group) individuals. Single-cell transcriptome landscapes of tumor samples were profiled. Subsequently, the differences in TME composition, functional phenotype of clusters, and cell-cell communications between the two groups were systematically analyzed.