{
  "abstract": "Background: Heterogeneous responses across disease sites may occur after systemic therapy for biliary tract cancer (BTC), but their pathological and immune features remain poorly characterized. We report a case with pathological complete response (pCR) at the primary and pulmonary metastatic sites but persistent nodal disease after sequential chemotherapy and immunotherapy.\n\nCase presentation: A man in his 50s with metastatic perihilar cholangiocarcinoma received gemcitabine plus cisplatin. Cisplatin was discontinued because of an allergic reaction without radiographic progression, followed by gemcitabine plus durvalumab, gemcitabine alone, and durvalumab maintenance. Resection demonstrated pCR in the primary biliary lesion and a pulmonary metastasis, whereas viable carcinoma persisted in 3 of 22 regional lymph nodes. All three metastatic lymph nodes showed prominent keratinizing squamous differentiation with p40 expression and loss of CK7 expression. Spatial analysis of one lymph node showed higher CD8-positive cell abundance at the tumor margin than in the core by both positive-cell proportion and cell density. FoxP3-positive cells also showed a margin-predominant distribution, whereas LAG-3 expression and PD-L1 H-score were higher in the core and TIM-3 was broadly distributed. Another lymph node showed a different CD8 distribution, indicating inter-nodal heterogeneity.\n\nConclusion: This case shows site-specific pathological heterogeneity after chemoimmunotherapy for BTC, with persistent nodal disease despite pCR at the primary and pulmonary metastatic sites. Residual nodal metastases showed keratinizing squamous differentiation and inter-nodal heterogeneity in immune-cell distribution. Because paired pretreatment nodal tissue, molecular or clonality analyses, cell type-specific checkpoint assessment, and spatial immune profiling were unavailable, the biological basis and generalizability remain unresolved.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University",
    "Department of Clinical Oncology, Jichi Medical University Hospital",
    "Department of Diagnostic Pathology, Jichi Medical University Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hideki Sasanuma"
    },
    {
      "affs": [
        0
      ],
      "name": "Keita Suto"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuki Kimura"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuichi Aoki"
    },
    {
      "affs": [
        0
      ],
      "name": "Masanobu Taguchi"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoya Kasahara"
    },
    {
      "affs": [
        0
      ],
      "name": "Kazue Morishima"
    },
    {
      "affs": [
        1
      ],
      "name": "Hideyuki Ohzawa"
    },
    {
      "affs": [
        2
      ],
      "name": "Naoki Sano"
    },
    {
      "affs": [
        2
      ],
      "name": "Noriyoshi Fukushima"
    },
    {
      "affs": [
        0
      ],
      "name": "Hironori Yamaguchi"
    },
    {
      "affs": [
        0
      ],
      "name": "Naohiro Sata"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8e1a4nxv7p3gv.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1855354",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1855354/full",
  "id": "8e1a4nxv7p3gv",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1855354/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",
      "RC581-607"
    ],
    [
      "openalex",
      "2746|Cholangiocarcinoma and Gallbladder Cancer Studies"
    ]
  ],
  "openalex": "W7223280784",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1855354/pdf",
  "pmcid": "PMC13739777",
  "pmid": "42996722",
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8e1a4nxv7p3gv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1855354",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1855354/full"
    },
    {
      "first_seen": "2026-10-30T13:43:47Z",
      "native_id": "3f592f16d4b24ac2aa19af829e4d0ab4",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fimmu.2026.1855354"
    },
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42996722",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996722"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholangiocarcinoma and Gallbladder Cancer Studies",
      "subfield": "surgery"
    }
  ],
  "title": "Persistent nodal disease with squamous differentiation and spatial immune heterogeneity after chemoimmunotherapy in biliary tract cancer: a high-resolution pathological analysis",
  "title_text": "Persistent nodal disease with squamous differentiation and spatial immune heterogeneity after chemoimmunotherapy in biliary tract cancer: a high-resolution pathological analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/8e1a4nxv7p3gv",
  "venue": "Frontiers in Immunology",
  "versions": []
}