{
  "abstract": "Tumour-derived extracellular vesicles (EVs) or exosomes are critical mediators of the cancer-immune system crosstalk, yet the mechanisms by which they reprogram neutrophil function in vivo remain insufficiently characterised. Here, we identify the serine protease inhibitor Serpin A1 as a predominant cargo component of small EVs (sEVs) released by head and neck cancer cels (HNC) and show that this molecule is both necessary and sufficient to confer a stable pro-tumoural programming of neutrophils. Uptake of Serpin A1-enriched sEVs elicits extensive proteomic remodelling in neutrophils including activation of STAT3 signalling, leading to sustained induction of PD-L1, increased Arginase 1 production and prolonged neutrophil lifespan. Functionally, these reprogrammed neutrophils acquire a capacity to drive epithelial-mesenchymal transition in tumour cells, and to impose exhaustion of T cells via metabolic restriction and arginine depletion, leading to their reduced cytotoxicity. Genetic ablation of Serpin A1 from tumour-derived sEVs or pharmacologic inhibition of serpin-STAT3 axis restores neutrophil anti-tumour functions. Collectively, these findings delineate a Serpin A1-STAT3/Arginase 1 as an important signalling pathway through which tumour-derived sEVs promote neutrophil-dependent immune suppression and tumour progression, and highlight EV-associated serpins as potential targets for future therapeutic intervention in cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.",
    "Department of Dermatology and Allergy, LMU Hospital, Ludwig-Maximilians-University, Munich, Germany.",
    "German Cancer Consortium (DKTK) Partner Site Düsseldorf/Essen, Essen, Germany.",
    "Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland.",
    "Department of Pediatrics III, University Children's Hospital of Essen, University of Duisburg-Essen, Essen, Germany.",
    "German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.",
    "Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.",
    "Exosome Research Lab (ERL), Department of Gastroenterology Hepatology and Transplantation Medicine, University of Duisburg-Essen, Essen, Germany.",
    "Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.",
    "Department of Radiology, Medical University of Gdansk, Gdańsk, Poland."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Maksim Domnich",
      "orcid": "0000-0003-4954-5418"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ekaterina Pylaeva",
      "orcid": "0000-0002-3941-9664"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Siakaeva",
      "orcid": "0000-0002-5607-2033"
    },
    {
      "affs": [
        0
      ],
      "name": "Nastassia Kabankova"
    },
    {
      "affs": [
        3
      ],
      "name": "Agnieszka Bedzinska"
    },
    {
      "affs": [
        3
      ],
      "name": "Damian Sojka"
    },
    {
      "affs": [
        3
      ],
      "name": "Aneta Zebrowska",
      "orcid": "0000-0001-6049-301X"
    },
    {
      "affs": [
        3
      ],
      "name": "Marta Gawin",
      "orcid": "0000-0002-2834-5129"
    },
    {
      "affs": [
        4
      ],
      "name": "Maren Soldierer",
      "orcid": "0009-0002-7021-3143"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaping Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Malwina Rist"
    },
    {
      "affs": [
        3
      ],
      "name": "Daniel Fochtman",
      "orcid": "0000-0002-0754-7012"
    },
    {
      "affs": [
        5
      ],
      "name": "Bernd Giebel",
      "orcid": "0000-0003-2446-948X"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Iris Helfrich",
      "orcid": "0000-0001-6150-9570"
    },
    {
      "affs": [
        0
      ],
      "name": "Ilona Thiel"
    },
    {
      "affs": [
        7
      ],
      "name": "Basant Kumar Thakur",
      "orcid": "0000-0001-7013-7895"
    },
    {
      "affs": [
        0
      ],
      "name": "Cornelius H L Kürten",
      "orcid": "0000-0002-2720-0075"
    },
    {
      "affs": [
        4
      ],
      "name": "Helmut Hanenberg"
    },
    {
      "affs": [
        8
      ],
      "name": "Sonja Ludwig",
      "orcid": "0000-0001-9751-323X"
    },
    {
      "affs": [
        9
      ],
      "name": "Piotr Widlak",
      "orcid": "0000-0001-5099-4726"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Stephan Lang",
      "orcid": "0009-0000-4420-9664"
    },
    {
      "affs": [
        3
      ],
      "name": "Monika Pietrowska",
      "orcid": "0000-0001-9317-7822"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jadwiga Jablonska",
      "orcid": "0000-0003-1490-2542"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e87jve5fq4z67.bib",
  "cited_by": 1,
  "doi": "10.1002/jev2.70385",
  "fulltext_url": "https://europepmc.org/articles/PMC13725528",
  "id": "e87jve5fq4z67",
  "issns": [
    "2001-3078"
  ],
  "landing_url": "https://europepmc.org/article/MED/42969065",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W4408215523",
  "pdf_url": "https://europepmc.org/articles/PMC13725528?pdf=render",
  "pmcid": "PMC13725528",
  "pmid": "42969065",
  "published": "2026-11-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/e87jve5fq4z67.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42969065",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42969065"
    },
    {
      "first_seen": "2026-11-04T12:23:53Z",
      "native_id": "PMC13725528",
      "source": "pmc",
      "url": "https://doi.org/10.1002/jev2.70385"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Serpin A1 Cargo Within Tumour-Derived Extracellular Vesicles Supports Pro-Tumoural Bias of Neutrophils in Cancer.",
  "title_text": "Serpin A1 Cargo Within Tumour-Derived Extracellular Vesicles Supports Pro-Tumoural Bias of Neutrophils in Cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:45Z",
  "url": "https://research.draconitic.com/paper/e87jve5fq4z67",
  "venue": "Journal of extracellular vesicles",
  "versions": []
}