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<p>The tumor microenvironment evolves during tumor development and influences the cells in the microenvironment to orchestrate a supportive environment for tumor growth. Here we collected 4,483,367 cells across 36 cancer types and constructed a pan-cancer resource named TabulaTIME. Our integrated analyses reveal that <i>CTHRC1</i> is a hallmark of extracellular matrix-related cancer-associated fibroblasts (CAFs) that are enriched in different cancer types. Spatiotemporal analyses further indicated that <i>CTHRC1</i><sup>+</sup> CAFs are located at the leading edge between the malignant and normal regions, potentially preventing immune infiltration. Moreover, we identified that <i>SLPI</i><sup>+</sup> macrophages exhibit profibrotic-associated phenotypes and colocalize with <i>CTHRC1</i><sup>+</sup> CAFs to form unique spatial ecotypes. Finally, we demonstrated that TabulaTIME can be used to analyze tumor ecotype composition and can serve as a reference for cell-type annotation. This work establishes a comprehensive single-cell landscape of the heterogenous TME and offers a potential therapeutic strategy for targeting the profibrotic ecotype in cancer treatment.</p>

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Spatiotemporal analyses of the pan-cancer single-cell landscape reveal widespread profibrotic ecotypes associated with tumor immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月25日

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  • Ya Han,
  • Lele Zhang,
  • Dongqing Sun,
  • Guangxu Cao,
  • Yuting Wang,
  • Jiali Yue,
  • Junjie Hu,
  • Zhonghua Dong,
  • Fang Li,
  • Taiwen Li,
  • Peng Zhang,
  • Qiu Wu,
  • Chenfei Wang

摘要

The tumor microenvironment evolves during tumor development and influences the cells in the microenvironment to orchestrate a supportive environment for tumor growth. Here we collected 4,483,367 cells across 36 cancer types and constructed a pan-cancer resource named TabulaTIME. Our integrated analyses reveal that CTHRC1 is a hallmark of extracellular matrix-related cancer-associated fibroblasts (CAFs) that are enriched in different cancer types. Spatiotemporal analyses further indicated that CTHRC1+ CAFs are located at the leading edge between the malignant and normal regions, potentially preventing immune infiltration. Moreover, we identified that SLPI+ macrophages exhibit profibrotic-associated phenotypes and colocalize with CTHRC1+ CAFs to form unique spatial ecotypes. Finally, we demonstrated that TabulaTIME can be used to analyze tumor ecotype composition and can serve as a reference for cell-type annotation. This work establishes a comprehensive single-cell landscape of the heterogenous TME and offers a potential therapeutic strategy for targeting the profibrotic ecotype in cancer treatment.