Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches
Xiongfeng Chen, Zhuan Zhou, Luyu Xie, Kailiang Qiao, Yiyue Jia, Si Liu, Zeynep Yazgan, Francesca Rossi, Yang Liu, Bo Zhang, Patricio M. Polanco, Herbert J. Zeh, Alex C. Kim, Huocong Huang
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.