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 ZhangLi Yang, Yong Peng, Lunzhi Dai, Hongbo Hu, Yong Jiang, Yiguo Hu, Jingqiang Zhu, Hong Jiang, Zhihui Li, Carlos Caulin, Jihwan Park, Heng Xu

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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/.

Original languageEnglish (US)
Article number6619
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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