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
{"title":"抗原呈递癌相关成纤维细胞龛的单细胞分辨率空间分析","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","doi":"10.1016/j.ccell.2025.09.001","DOIUrl":null,"url":null,"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.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"64 1","pages":""},"PeriodicalIF":44.5000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"doi\":\"10.1016/j.ccell.2025.09.001\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":9670,\"journal\":{\"name\":\"Cancer Cell\",\"volume\":\"64 1\",\"pages\":\"\"},\"PeriodicalIF\":44.5000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ccell.2025.09.001\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.09.001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches
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.
期刊介绍:
Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows:
Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers.
Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice.
Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers.
Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies.
Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.