标题：Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non–small-cell lung carcinoma
摘要：SummaryMalignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non–small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulatedGNB2L1andCAV1expression were enriched in the EGFR TKI-resistant group. Moreover,GZMKupregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC.Graphical abstractDisplay OmittedHighlights•ScRNA-seq reveals associations between cellular plasticity and EGFR-TKI response•Lung epithelial progenitor-like cells are abundant in the TKI-resistant group•HLA-II gene expression are upregulated in the epithelial cells of TKI-sensitive group•Immunosuppressive TME was associated with the TKI resistance in NSCLCCancer; Immunology; Omics; Transcriptomics
