2. Academic Validation
  3. Antigen-presenting CAFs orchestrate immunosuppressive niches via CXCL13-mediated immune cell infiltration dysregulation and prognostic stratification in triple-negative breast cancer

Antigen-presenting CAFs orchestrate immunosuppressive niches via CXCL13-mediated immune cell infiltration dysregulation and prognostic stratification in triple-negative breast cancer

  • Int Immunopharmacol. 2025 Sep 23:162:115193. doi: 10.1016/j.intimp.2025.115193.
Jinying Tian 1,  Ye Li 2,  Zijin Wang 3,  Yuting Zhong 4,  Yan Yao 5,  Changgang Sun 6
Affiliations

Affiliations

  • 1 College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China; School of Public Health, Shandong Second Medical University, Weifang, China.
  • 2 Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macao Special Administrative Region of China, China; College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 3 Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining, China.
  • 4 School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 5 Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, China; College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang, China.
  • 6 Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, China; College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang, China. Electronic address: zyxyscg@sdsmu.edu.cn.
PMID: 40633212 DOI: 10.1016/j.intimp.2025.115193
Abstract

Antigen-presenting cancer-associated fibroblasts (apCAFs) are a recently identified stromal cell subset in the tumor microenvironment, playing a significant role in tumor immune regulation through their unique antigen-presenting function. This study aimed to elucidate the biological significance of apCAFs in triple-negative breast Cancer (TNBC) by analyzing single-cell transcriptomic data from nine TNBC patients in public databases and integrating TCGA data. Three major CAF subpopulations were identified, with apCAFs primarily establishing functional connections with various cell types, including T cells, via the MIF signaling pathway. Based on genes significantly associated with overall survival, TNBC patients were stratified into two subgroups (C1 and C2), with the C1 group exhibiting stronger immune response activity. A prognostic risk model was constructed using four key genes (CXCL13, LOXL1, PLOD2, and CIR1), demonstrating that the low-risk group had higher levels of immune cell infiltration and immune function activity. Among these genes, CXCL13 showed the most significant correlation with patient overall survival, and its significant upregulation in apCAFs was experimentally validated, suggesting its crucial role in TNBC prognosis and immune regulation. The survival prediction model based on these four apCAF-related prognostic genes has shown significant potential in evaluating TNBC patient prognosis and predicting immunotherapy efficacy. Furthermore, this study provides important theoretical evidence for a deeper understanding of the role of apCAFs in the classification of breast Cancer subtypes.

Keywords

Antigen-presenting cancer-associated fibroblasts; Prognostic model; Triple-negative breast cancer; Tumor immune regulation.

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