Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer

• DOI: 10.1038/s41467-021-22801-0
• Publication Date: 2021-05-05T10:04:15Z
• Authors: Fengying Wu; Jue Fan; Yayi He; Anwen Xiong; Jia Yu; Yixin Li; Yan Zhang; Wencheng Zhao; Fei Zhou; Wei Li; Jie Zhang; Xiaosheng Zhang; Meng Qiao; Guanghui Gao; Shanhao Chen; Xiaoxia Chen; Xuefei Li; Likun Hou; Chunyan Wu; Chunxia Su; Shengxiang Ren; Margarete Odenthal; Reinhard Buettner; Nan Fang; Caicun Zhou
• Keywords: 0301 basic medicine; Lung Neoplasms; Science; Q; Epithelial Cells; Article; 3. Good health; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Carcinoma, Squamous Cell; Tumor Microenvironment; Humans; Th17 Cells; Transcriptome; Lung

AbstractLung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.