Single-Cell Resolution Spatial Analysis of Antigen-Presenting Cancer-Associated Fibroblast Niches

Authors

• Xiongfeng Chen
• Zhuan Zhou
• Luyu Xie
• Kailiang Qiao
• Yiyue Jia
• Shunheng Liu
• Zeynep Yazgan
• Francesca Rossi
• Yang Liu
• Bo Zhang
• Patricio M Polanco
• Herbert J Zeh
• Alex C Kim
• Huocong Huang

Language

English

Publication Date

12-8-2025

Journal

Cancer Cell

DOI

10.1016/j.ccell.2025.09.001

PMID

41005303

PMCID

PMC12479095

PubMedCentral® Posted Date

9-25-2026

PubMedCentral® Full Text Version

Author MSS

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 Fibroblasts, Humans, Single-Cell Analysis, Animals, Mice, Tumor Microenvironment, Neoplasms, Antigen-Presenting Cells, Antigen Presentation, cancer-associated fibroblast, peritoneal metastasis, pancreatic cancer, mesothelial cell, fibrocyte

Published Open-Access

yes

Recommended Citation

Chen, Xiongfeng; Zhou, Zhuan; Xie, Luyu; et al., "Single-Cell Resolution Spatial Analysis of Antigen-Presenting Cancer-Associated Fibroblast Niches" (2025). Faculty, Staff and Student Publications. 6857.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6857