{
  "abstract": "Cancer-associated fibroblasts (CAFs) exhibit remarkable functional heterogeneity, with conserved subtypes observed across diverse malignancies. However, their shared roles in shaping the tumor microenvironment (TME) and their dynamic plasticity remain incompletely understood. In this study, through integrated single-cell and spatial transcriptomic profiling across four cancer types, we identified two distinct immunomodulatory CAF states, termed antigen-presenting CAFs (apCAFs) and matrix-producing CAFs (mCAFs). Across multiple solid tumors, apCAFs were associated with enhanced anti-tumor immune features and favorable prognosis, whereas mCAFs were associated with immunosuppressive characteristics and poorer clinical outcomes. Spatial analyses revealed distinct localization patterns of apCAFs and mCAFs within the TME. Functionally, patient-derived apCAFs promoted T-cell migration, proliferation, and activation, whereas mCAFs suppressed these responses in vitro. Pan-cancer analyses further revealed a strong inverse correlation between apCAF and mCAF abundance across tumor tissues. Mechanistically, IFN-γ and TGF-β-associated signaling contexts were linked to distinct CAF transcriptional programs, with IFN-γ promoting apCAF-associated features and TGF-β favoring mCAF-associated features, suggesting a potential role of cytokine context in shaping CAF state heterogeneity. Clinically, apCAFs correlated with favorable immunotherapy response, whereas mCAFs predicted poor therapeutic outcomes. Collectively, these findings identify conserved immunomodulatory CAF subtypes across cancers, reveal distinct cytokine-associated CAF programs, and support stromal reprogramming as a promising strategy to enhance immunotherapy efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.",
    "Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.",
    "Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.",
    "Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.",
    "Endoscopy Center and Endoscopy Research Institute, Shanghai Collaborative Innovation Center of Endoscopy, Zhongshan Hospital, Fudan University, Shanghai, China.",
    "Department of Ultrasound, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.",
    "Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Key Laboratory of Gut Microecology, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. qinhuanlong@tongji.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Feifei Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Qi Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Dengfeng Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Youhua Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongyan Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Rao"
    },
    {
      "affs": [
        0
      ],
      "name": "Man Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaohui Gao"
    },
    {
      "affs": [
        3
      ],
      "name": "Renfeng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiyuan Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shufei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiao Jiang"
    },
    {
      "affs": [
        4
      ],
      "name": "Shengli Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Dexi Bi"
    },
    {
      "affs": [
        5
      ],
      "name": "Haixian Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qing Wei",
      "orcid": "0000-0002-9990-2535"
    },
    {
      "affs": [
        6
      ],
      "name": "Huanlong Qin",
      "orcid": "0000-0002-9315-5866"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5gasfmz4he5wm.bib",
  "cited_by": 0,
  "doi": "10.1038/s41392-026-02965-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13680625",
  "id": "5gasfmz4he5wm",
  "issns": [
    "2095-9907",
    "2059-3635"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897126",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "lcc",
      "QH301-705.5"
    ],
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      "lcc",
      "R"
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      "1312|TGF-β signaling in diseases"
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  "pdf_url": "https://europepmc.org/articles/PMC13680625?pdf=render",
  "pmcid": "PMC13680625",
  "pmid": "42897126",
  "published": "2026-10-20",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/5gasfmz4he5wm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42897126",
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      "url": "https://doi.org/10.1038/s41392-026-02965-1"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|TGF-β signaling in diseases",
      "subfield": "molecular-biology"
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  ],
  "title": "Cytokine context shapes antigen-presenting and matrix-producing states of cancer-associated fibroblasts.",
  "title_text": "Cytokine context shapes antigen-presenting and matrix-producing states of cancer-associated fibroblasts.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:35Z",
  "url": "https://research.draconitic.com/paper/5gasfmz4he5wm",
  "venue": "Signal transduction and targeted therapy",
  "versions": []
}