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Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer

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资源类型：
Pubmed体系：
作者：
Lu Xunxi[1,2] * ; Gou Zongchao[3] * ; Chen Hong[4] ; Li Li[4] ; Chen Fei[4] ; Bao Chunjuan[4] ; Bu Hong[1,2] ; Zhang Zhang[1,2] ;
机构： [1]Department of Pathology, West China Hospital, Sichuan University, Chengdu, PR China. [2]Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, PR China. [3]Breast Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, PR China. [4]Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, PR China.
出处：
DOI： 10.1002/path.6395
ISSN：

关键词： triple-negative breast cancer tumor microenvironment extracellular matrix cancer-associated fibroblasts macrophages immunotherapy

摘要：
The impact of high heterogeneity of cancer-associated fibroblasts (CAFs) on triple-negative breast cancer (TNBC) immunotherapy response has not been fully elucidated, restricting progress in precision immuno-oncology. We integrated single-cell transcriptomic data from 18 TNBC patients and analyzed fibroblast subpopulations. Extracellular matrix CAFs (ecmCAFs) were identified as a fibroblast subpopulation with distinct ECM-associated characteristics. The ecmCAFs were significantly enriched in TNBC patients with residual disease after neoadjuvant immunotherapy and contributed to a fibrotic tumor microenvironment and T-cell exclusion. Secreted phosphoprotein 1 (SPP1) positive macrophages (SPP1+ Mφs) were closely localized to ecmCAFs and produced more transforming growth factor beta (TGFB1), interleukin 1 beta (IL1B), and SPP1 under hypoxic conditions. SPP1+ Mφs were found to facilitate the differentiation of normal breast fibroblasts to ecmCAFs, thus promoting ECM remodeling and stromal fibrosis. Our work revealed the critical role of ecmCAFs in generating a desmoplastic architecture and driving immunosuppression in TNBC. © 2025 The Pathological Society of Great Britain and Ireland.© 2025 The Pathological Society of Great Britain and Ireland.

基金：
This work was supported by the National Natural Science Foundation of PR China (82404677), Post- Doctor Research Project, West China Hospital, Sichuan University (2021HXBH080), Sichuan Science and Technology Program (No. 2024YFFK0394).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
无
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 病理学 2 区 肿瘤学
第一作者：
第一作者机构： [1]Department of Pathology, West China Hospital, Sichuan University, Chengdu, PR China. [2]Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, PR China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pathology, West China Hospital, Sichuan University, Chengdu, PR China. [2]Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, PR China.
推荐引用方式(GB/T 7714)：
Lu Xunxi,Gou Zongchao,Chen Hong,et al.Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer[J].The Journal Of Pathology.2025,doi:10.1002/path.6395.
APA：
Lu Xunxi,Gou Zongchao,Chen Hong,Li Li,Chen Fei...&Zhang Zhang.(2025).Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer.The Journal Of Pathology,,
MLA：
Lu Xunxi,et al."Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer".The Journal Of Pathology .(2025)

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