Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 25:S1535-6108(25)00393-9.
doi: 10.1016/j.ccell.2025.09.001. Online ahead of print.

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

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

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

Xiongfeng Chen et al. Cancer Cell. .

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.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

    1. Younesi FS, Miller AE, Barker TH, Rossi FMV, and Hinz B (2024). Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nat Rev Mol Cell Biol 25, 617–638. 10.1038/s41580-024-00716-0. - DOI - PubMed
    1. Buechler MB, Pradhan RN, Krishnamurty AT, Cox C, Calviello AK, Wang AW, Yang YA, Tam L, Caothien R, Roose-Girma M, et al. (2021). Cross-tissue organization of the fibroblast lineage. Nature 593, 575–579. 10.1038/s41586-021-03549-5. - DOI - PubMed
    1. Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, Driskell RR, Rosenthal N, Biernaskie J, and Horsley V (2021). Fibroblasts: Origins, definitions, and functions in health and disease. Cell 184, 3852–3872. 10.1016/j.cell.2021.06.024. - DOI - PMC - PubMed
    1. Dvorak HF (2015). Tumors: wounds that do not heal-redux. Cancer Immunol Res 3, 1–11. 10.1158/2326-6066.CIR-14-0209. - DOI - PMC - PubMed
    1. Caligiuri G, and Tuveson DA (2023). Activated fibroblasts in cancer: Perspectives and challenges. Cancer Cell 41, 434–449. 10.1016/j.ccell.2023.02.015. - DOI - PMC - PubMed

LinkOut - more resources