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  3. Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches

Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches

  • Cancer Cell. 2025 Sep 25:S1535-6108(25)00393-9. doi: 10.1016/j.ccell.2025.09.001.
Xiongfeng Chen 1,  Zhuan Zhou 1,  Luyu Xie 2,  Kailiang Qiao 3,  Yiyue Jia 1,  Shunheng Liu 4,  Zeynep Yazgan 4,  Francesca Rossi 5,  Yang Liu 6,  Bo Zhang 6,  Patricio M Polanco 5,  Herbert J Zeh 3rd 5,  Alex C Kim 7,  Huocong Huang 8
Affiliations

Affiliations

  • 1 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 2 Department of Health Data Science and Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 4 Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 6 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 7 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: alex.kim@utsouthwestern.edu.
  • 8 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: huocong.huang@utsouthwestern.edu.
PMID: 41005303 DOI: 10.1016/j.ccell.2025.09.001
Abstract

Recent studies identify a unique subtype of cancer-associated fibroblasts (CAFs) termed antigen-presenting CAFs (apCAFs), which remain poorly understood. To gain a comprehensive understanding of the origin and function of apCAFs, we construct a fibroblast molecular atlas across 15 types of tissues and solid tumors. Our integration study unexpectedly reveals two distinct apCAF populations present in most Cancer types: one associated with mesothelial-like cells and the Other with fibrocytes. Using a high-resolution single-cell spatial imaging platform, we characterize the spatial niches of these apCAF populations. We find that mesothelial-like apCAFs are located near Cancer cells, while fibrocyte-like apCAFs are associated with lymphocyte-enriched niches. Additionally, we discovered that both apCAF populations can up-regulate secreted phosphoprotein 1 (SPP1), which facilitates primary tumor formation, peritoneal metastasis, and therapy resistance. Taken together, this study offers an unprecedented resolution in analyzing apCAFs and their spatial niches.

Keywords

cancer-associated fibroblast; fibrocyte; mesothelial cell; pancreatic cancer; peritoneal metastasis.

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