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

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  • Han Luo

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Xuyang Xia

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Li-Bin Huang

    (West China Hospital, Sichuan University
    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
    West China Hospital, Sichuan University)

  • Wei-Han Zhang

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Yang Shu

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Xiangyu Kong

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Zhixiang Ren

    (West China Hospital, Sichuan University)

  • Pei-Heng Li

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Yang Liu

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Huairong Tang

    (West China Hospital, Sichuan University)

  • Ronghao Sun

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University
    University of Electronic Science and Technology of China)

  • 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
    West China Hospital, Sichuan University)

  • Jingqiang Zhu

    (West China Hospital, Sichuan University
    West China Hospital, Sichuan University)

  • Hong Jiang

    (West China Hospital, Sichuan University)

  • Zhihui Li

    (West China Hospital, Sichuan University
    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
    West China Hospital, Sichuan University)

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/ .

Suggested Citation

  • 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 & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34395-2
    DOI: 10.1038/s41467-022-34395-2
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    6. Z. L. Liu & X. Y. Meng & R. J. Bao & M. Y. Shen & J. J. Sun & W. D. Chen & F. Liu & Y. He, 2024. "Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
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