{
  "abstract": "Pancreatic ductal carcinoma (PDAC) is characterized by a highly immunosuppressive, extracellular matrix-rich microenvironment, yet tumours display marked heterogeneity1–4. This raises the question of whether immune resistance is a global tumour property or is organized within spatially restricted niches. Here, using Perturb-map spatial functional genomics, we determine how different genes shape the growth and cellular environments of PDAC clones across space and time. This analysis revealed early gene-driven remodelling of local immune neighbourhoods preceding late-stage spatial clonal dominance. We identify SERPINE1 (encoding plasminogen activator inhibitor 1 (PAI1)) and SERPINB2 (encoding PAI2) as dominant regulators of tumour microenvironment control and immune evasion. These serpins promote stabilization of fibrin-rich extracellular matrix niches that spatially retain and programme macrophages towards immunosuppressive states while excluding cytotoxic T cells. Loss of Serpine1 or Serpinb2, or pharmacological inhibition of PAI1 or CD18, improves tumour control in mice and synergizes with anti-PD-1. Multimodal spatial analysis of patient tumours revealed that immunosuppressive niches form around rare SERPINB2- and SERPINE1-expressing PDAC subpopulations, dominated by SPP1+/MARCO+ macrophages. These findings identify cancer-derived SERPINE1 and SERPINB2 as local spatial organizers of immune suppression, linking tumour-intrinsic heterogeneity to local microenvironmental control and immunotherapy resistance in PDAC.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA",
    "Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA",
    "Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA",
    "Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chiara Falcomatà"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Maximilian M. Schaefer",
      "orcid": "0000-0002-6038-7847"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bhavya Singh",
      "orcid": "0000-0001-6641-6429"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Divya Chhamalwan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexander Tepper"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sebastian R. Nielsen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hunter T. Potak"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Maxime Dhainaut"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Gurkan Mollaoglu"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Matthew D. Park",
      "orcid": "0000-0003-3488-3262"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Miriam Merad",
      "orcid": "0000-0002-4481-7827"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Alessia Baccarini"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Brian D. Brown",
      "orcid": "0000-0002-3670-8778"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5gv5pexnvb6x0.bib",
  "cited_by": 0,
  "doi": "10.1038/s41586-026-11002-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13716829/",
  "id": "5gv5pexnvb6x0",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-11002-8",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7212019589",
  "pdf_url": null,
  "pmcid": "PMC13716829",
  "pmid": "42717081",
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5gv5pexnvb6x0.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:24:01Z",
      "native_id": "PMC13716829",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41586-026-11002-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "A serpin–myeloid axis in pancreatic cancer heterogeneity and immune evasion",
  "title_text": "A serpin–myeloid axis in pancreatic cancer heterogeneity and immune evasion",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:16Z",
  "url": "https://research.draconitic.com/paper/5gv5pexnvb6x0",
  "venue": "Nature",
  "versions": []
}