TY - JOUR
T1 - Single-cell transcriptomic profiling reveals the tumor heterogeneity of small-cell lung cancer
AU - Tian, Yanhua
AU - Li, Qingqing
AU - Yang, Zhenlin
AU - Zhang, Shu
AU - Xu, Jiachen
AU - Wang, Zhijie
AU - Bai, Hua
AU - Duan, Jianchun
AU - Zheng, Bo
AU - Li, Wen
AU - Cui, Yueli
AU - Wang, Xin
AU - Wan, Rui
AU - Fei, Kailun
AU - Zhong, Jia
AU - Gao, Shugeng
AU - He, Jie
AU - Gay, Carl M.
AU - Zhang, Jianjun
AU - Wang, Jie
AU - Tang, Fuchou
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Small-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.
AB - Small-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.
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U2 - 10.1038/s41392-022-01150-4
DO - 10.1038/s41392-022-01150-4
M3 - Article
C2 - 36195615
AN - SCOPUS:85139403419
SN - 2095-9907
VL - 7
JO - Signal Transduction and Targeted Therapy
JF - Signal Transduction and Targeted Therapy
IS - 1
M1 - 346
ER -