{
  "abstract": "Antigen-presenting cancer-associated fibroblasts (apCAFs), commonly defined by MHC class II molecules, CD74, and related transcriptional programs, exhibit divergent functions across gastrointestinal tumors. In pancreatic ductal adenocarcinoma, mesothelium-derived apCAFs promote regulatory T-cell differentiation and suppress effector responses, whereas their abundance in gastric cancer is associated with earlier-stage disease, longer survival, and improved immunotherapy responses. This paradox may reflect microenvironmental context and classifications that conflate transcriptional state, cellular origin, and immune function. apCAFs may therefore represent reversible, context-dependent states defined by origin, MHC class II-restricted antigen presentation, and co-stimulatory capacity. We propose a two-layer model that has not been validated in apCAFs. In this model, the chromatin accessibility of CIITA, CD40, CD80, and CD86 constructs a functional licensing range, while interferon - γ (IFN - γ), interleukin-1 (IL-1), and transforming growth factor - β (TGF - β) guide the formation of specific phenotypes within this range. Insufficient co-stimulation may favor immune tolerance; activation of co-stimulatory programs may support CD4 ⁺ T-cell help and CD8 ⁺ T-cell infiltration. Treatment-induced changes in CAF composition may reflect selective survival or genuine state transitions. Distinguishing these mechanisms requires lineage tracing, longitudinal single-cell transcriptomic and chromatin profiling, and patient-derived organoid–fibroblast co-cultures. Neoadjuvant therapy and serial endoscopic sampling provide feasible settings for capturing transient states. This framework supports replacing broad CAF depletion with temporally and state-informed functional reprogramming.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine",
    "The First Clinical Medical College, Guizhou University of Traditional Chinese Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhilin Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Dingnan Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenxiang An"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bx67ht7mhd02a.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.2000409",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.2000409/full",
  "id": "bx67ht7mhd02a",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.2000409/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223667504",
  "pdf_url": "https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.2000409/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bx67ht7mhd02a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.2000409",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.2000409/full"
    },
    {
      "first_seen": "2026-10-30T13:47:18Z",
      "native_id": "222692c9f58d4edb8f1d758b86dcf3ad",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fonc.2026.2000409"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Subtype or state? Rethinking the apCAF paradox and fibroblast plasticity in gastrointestinal cancers",
  "title_text": "Subtype or state? Rethinking the apCAF paradox and fibroblast plasticity in gastrointestinal cancers",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:18Z",
  "url": "https://research.draconitic.com/paper/bx67ht7mhd02a",
  "venue": "Frontiers in Oncology",
  "versions": []
}