{
  "abstract": "Although hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) arise in the same organ, they occupy distinct immune geographies within a shared barrier network. HCC is relatively enriched for inflamed yet dysfunctional CD8 ⁺ T-cell states, whereas iCCA is more often characterized by stromal- and myeloid-associated immune exclusion; both patterns can occur in either tumor, but differ in their relative predominance. Immune checkpoint blockade has reshaped the treatment landscape in primary liver cancer, but durable benefit remains limited and heterogeneous. Here, we place the T-cell landscape—not checkpoint expression alone—at the center of comparison, focusing on where tumor-reactive cells reside, the states they occupy, and the factors that constrain their reactivation. By integrating clinical and translational evidence across HCC and iCCA, and distinguishing throughout between mechanisms established in human tumors and those extrapolated from experimental models or from other malignancies, we propose that differences in the T-cell landscape help explain divergent therapeutic responses and provide a testable framework for biomarker-guided combination strategies. The key question is therefore not simply whether to release the checkpoint, but what each tumor’s T-cell ecosystem requires for effective reactivation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, The First Affiliated Hospital of Yangtze University",
    "Clinical Molecular Immunology Center, Department of Immunology, School of Medicine, Yangtze University",
    "Department of Hepatobiliary Surgery, The First Affiliated Hospital of Yangtze University, The First People’s Hospital of Jingzhou"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "YanXi Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Tao Peng"
    },
    {
      "affs": [
        1
      ],
      "name": "Hao Nie"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2h28cj19mphzz.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1944650",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720682/?tool=EBI",
  "id": "2h28cj19mphzz",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944650/full",
  "language": "eng",
  "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": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7222513806",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1944650/pdf",
  "pmcid": "PMC13720682",
  "pmid": "42964795",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2h28cj19mphzz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1944650",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944650/full"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720682",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720682"
    },
    {
      "first_seen": "2026-11-03T12:21:31Z",
      "native_id": "PMC13720682",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1944650"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Same organ, divergent immunity: T-cell exhaustion versus stromal exclusion in hepatocellular carcinoma and intrahepatic cholangiocarcinoma",
  "title_text": "Same organ, divergent immunity: T-cell exhaustion versus stromal exclusion in hepatocellular carcinoma and intrahepatic cholangiocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:31Z",
  "url": "https://research.draconitic.com/paper/2h28cj19mphzz",
  "venue": "Frontiers in Immunology",
  "versions": []
}