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

TitlePan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.
Publication TypeJournal Article
Year of Publication2022
AuthorsLuo H, Xia X, Bin Huang L-, An H, Cao M, Kim GDae, Chen H-N, Zhang W-H, Shu Y, Kong X, Ren Z, Li P-H, Liu Y, Tang H, Sun R, Li C, Bai B, Jia W, Liu Y, Zhang W, Yang L, Peng Y, Dai L, Hu H, Jiang Y, Hu Y, Zhu J, Jiang H, Li Z, Caulin C, Park J, Xu H
JournalNat Commun
Volume13
Issue1
Pagination6619
Date Published2022 Nov 04
ISSN2041-1723
KeywordsCancer-Associated Fibroblasts, Fibroblasts, Humans, Macrophages, Neoplasms, Single-Cell Analysis, Tumor Microenvironment
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/ .

DOI10.1038/s41467-022-34395-2
Alternate JournalNat Commun
PubMed ID36333338
PubMed Central IDPMC9636408
Faculty Reference: 
Carlos Caulin, PhD