{
  "abstract": "Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB), although homologous recombination-deficient (HRD) tumors may derive benefit. In the POLAR trial of maintenance pembrolizumab plus olaparib after platinum-based chemotherapy for metastatic PC, responses remained heterogeneous. To define determinants of productive antitumor immunity, we integrated longitudinal blood TCR sequencing with tumor single-cell and spatial profiling. Durable benefit was associated with rare tumor-infiltrating, peripherally expanding (TIE) CD8+ T cell clonotypes, a subset of which were functionally neoantigen-reactive. TIE patients showed markedly prolonged survival beyond established genomic and immune biomarkers. Conversely, resistance was associated with spatial T cell exclusion, myCAF-rich stromal remodeling, basal-like/KRAS-associated malignant-cell programs, and expansion of CTLA4 regulatory T cells linked to local immunosuppressive remodeling. These findings define a clonotype-resolved framework for immune monitoring and identify complementary stromal, tumor-intrinsic, and regulatory immune barriers that may guide rational combination immunotherapy in PC.",
  "abstract_shown": true,
  "affiliations": [
    "David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Ket"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 42,
  "authors": [
    {
      "name": "M. Hilmi"
    },
    {
      "name": "J. D. Schoenfeld"
    },
    {
      "name": "W. McKerrow"
    },
    {
      "name": "Y. Elhanati"
    },
    {
      "name": "C. A. O'Connor"
    },
    {
      "name": "S. Umeda"
    },
    {
      "name": "N. Lecomte"
    },
    {
      "name": "J. P. Melchor"
    },
    {
      "name": "A. Cardenas"
    },
    {
      "name": "M. Lao"
    },
    {
      "name": "V. Nasca"
    },
    {
      "name": "E.-R. Karnoub"
    },
    {
      "name": "N. Tezcan"
    },
    {
      "name": "Z. Tarcan"
    },
    {
      "name": "J. F. Chou"
    },
    {
      "name": "R. Sharma"
    },
    {
      "name": "J. Song"
    },
    {
      "name": "M. May"
    },
    {
      "name": "F. Balogun"
    },
    {
      "name": "K. H. Yu"
    },
    {
      "name": "K. Soares"
    },
    {
      "name": "C. Reiche"
    },
    {
      "name": "M. Milighetti"
    },
    {
      "name": "D. Pe'er"
    },
    {
      "name": "S. A. Vardhana"
    },
    {
      "name": "M. Capanu"
    },
    {
      "name": "O. Basturk"
    },
    {
      "name": "B. Rousseau"
    },
    {
      "name": "Y. Wang"
    },
    {
      "name": "J. Lihm"
    },
    {
      "name": "N. Mohibullah"
    },
    {
      "name": "V. Rolston"
    },
    {
      "name": "E. Santos"
    },
    {
      "name": "M. Reyngold"
    },
    {
      "name": "A. Wei"
    },
    {
      "name": "V. Balachandran"
    },
    {
      "name": "M. H. Sherman"
    },
    {
      "name": "N. Riaz"
    },
    {
      "name": "C. Iacobuzio-Donahue"
    },
    {
      "name": "B. Greenbaum"
    },
    {
      "name": "E. M. O'Reilly"
    },
    {
      "affs": [
        0
      ],
      "name": "W. Park"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6nxe24d34x6m7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752426",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752426v1.full",
  "id": "6nxe24d34x6m7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752426v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7213592437",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752426v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6nxe24d34x6m7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:09Z",
      "native_id": "10.64898/2026.09.17.752426",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752426v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Neoantigen-reactive CD8+ T cell engagement marks exceptional survivors of pancreatic cancer",
  "title_text": "Neoantigen-reactive CD8+ T cell engagement marks exceptional survivors of pancreatic cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:09Z",
  "url": "https://research.draconitic.com/paper/6nxe24d34x6m7",
  "venue": "bioRxiv",
  "versions": []
}