Single-cell transcriptomic profiling reveals the tumor heterogeneity of small-cell lung cancer

• DOI: 10.1038/s41392-022-01150-4
• Publication Date: 2022-10-05T00:03:17Z
• Authors: Yanhua Tian; Qingqing Li; Zhenlin Yang; Shu Zhang; Jiachen Xu; Zhijie Wang; Hua Bai; Jianchun Duan; Bo Zheng; Wen Li; Yueli Cui; Xin Wang; Rui Wan; Kailun Fei; Jia Zhong; Shugeng Gao; Jie He; Carl M. Gay; Jianjun Zhang; Jie Wang; Fuchou Tang
• Keywords: 0301 basic medicine; Cancer Research; Lung Neoplasms; QH301-705.5; Epidemiology; Immunology; Cancer research; Cell cycle; Gene; Article; Small Cell Lung Cancer; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Health Sciences; Tumor Microenvironment; Gene signature; Genetics; Humans; Biology (General); Immune Checkpoint Inhibitors; Tumor Markers; Biology; FOS: Clinical medicine; R; Intratumor Heterogeneity; Epidemiology and Management of Neuroendocrine Tumors; Life Sciences; Small Cell Lung Carcinoma; Gene expression profiling; Genomic Landscape of Cancer and Mutational Signatures; 3. Good health; Immune system; Single-cell analysis; Phenotype; Oncology; Tumor microenvironment; FOS: Biological sciences; Medicine; Cell; Immune checkpoint; Gene expression; Immunotherapy; Small-Cell Lung Cancer; Lung cancer; Transcriptome; Transcription Factors

AbstractSmall-cell lung cancer (SCLC) is the most aggressive and lethal subtype of lung cancer, for which, better understandings of its biology are urgently needed. Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment (TME) and investigate their roles in tumorigenic processes. Here, we performed high-precision single-cell transcriptomic analysis of ~5000 individual cells from primary tumors (PTs) and matched normal adjacent tissues (NATs) from 11 SCLC patients, including one patient with both PT and relapsed tumor (RT). The comparison revealed an immunosuppressive landscape of human SCLC. Malignant cells in SCLC tumors exhibited diverse states mainly related to the cell cycle, immune, and hypoxic properties. Our data also revealed the intratumor heterogeneity (ITH) of key transcription factors (TFs) in SCLC and related gene expression patterns and functions. The non-neuroendocrine (non-NE) tumors were correlated with increased inflammatory gene signatures and immune cell infiltrates in SCLC, which contributed to better responses to immune checkpoint inhibitors. These findings indicate a significant heterogeneity of human SCLC, and intensive crosstalk between cancer cells and the TME at single-cell resolution, and thus, set the stage for a better understanding of the biology of SCLC as well as for developing new therapeutics for SCLC.