Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Han Luo (), Xuyang Xia, Li-Bin Huang, Hyunsu An, Minyuan Cao, Gyeong Dae Kim, Hai-Ning Chen, Wei-Han Zhang, Yang Shu, Xiangyu Kong, Zhixiang Ren, Pei-Heng Li, Yang Liu, Huairong Tang, Ronghao Sun, Chao Li, Bing Bai, Weiguo Jia, Yi Liu, Wei Zhang, Li Yang, Yong Peng, Lunzhi Dai, Hongbo Hu, Yong Jiang, Yiguo Hu, Jingqiang Zhu, Hong Jiang, Zhihui Li, Carlos Caulin, Jihwan Park () and Heng Xu ()
Additional contact information
Han Luo: West China Hospital, Sichuan University
Xuyang Xia: West China Hospital, Sichuan University
Li-Bin Huang: West China Hospital, Sichuan University
Hyunsu An: Gwangju Institute of Science and Technology (GIST)
Minyuan Cao: West China Hospital, Sichuan University
Gyeong Dae Kim: Gwangju Institute of Science and Technology (GIST)
Hai-Ning Chen: West China Hospital, Sichuan University
Wei-Han Zhang: West China Hospital, Sichuan University
Yang Shu: West China Hospital, Sichuan University
Xiangyu Kong: West China Hospital, Sichuan University
Zhixiang Ren: West China Hospital, Sichuan University
Pei-Heng Li: West China Hospital, Sichuan University
Yang Liu: West China Hospital, Sichuan University
Huairong Tang: West China Hospital, Sichuan University
Ronghao Sun: West China Hospital, Sichuan University
Chao Li: University of Electronic Science and Technology of China
Bing Bai: Kunming University of Science and Technology; Yunnan Key Laboratory of Primate Biomedical Research
Weiguo Jia: West China Hospital, Sichuan University
Yi Liu: West Chia Hospital, Sichuan University
Wei Zhang: Xiangya Hospital, Central South University
Li Yang: West China Hospital, Sichuan University
Yong Peng: West China Hospital, Sichuan University
Lunzhi Dai: West China Hospital, Sichuan University
Hongbo Hu: West China Hospital, Sichuan University
Yong Jiang: West China Hospital, Sichuan University
Yiguo Hu: West China Hospital, Sichuan University
Jingqiang Zhu: West China Hospital, Sichuan University
Hong Jiang: West China Hospital, Sichuan University
Zhihui Li: West China Hospital, Sichuan University
Carlos Caulin: Department of Otolaryngology - Head & Neck Surgery and University of Arizona Cancer Center, University of Arizona
Jihwan Park: Gwangju Institute of Science and Technology (GIST)
Heng Xu: West China Hospital, Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .

Date: 2022
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DOI: 10.1038/s41467-022-34395-2

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