{
  "abstract": "Background\n\nSerous ovarian carcinoma (SOC) is a highly aggressive gynaecological malignancy with frequent relapse and the development of chemoresistance. A major feature of SOC tumour microenvironment is the accumulation of dense collagen fibres, which promote tumour progression and immune evasion. Discoidin domain receptor 2 (DDR2), a collagen-binding receptor tyrosine kinase activated by fibrillar collagens, mediates extracellular matrix-associated signalling involved in tumour progression and immune exclusion. However, its role in limiting antitumour immunity and contributing to immunotherapy resistance in SOC remains poorly understood.Methods\n\nWe investigated the impact of DDR2 blockade on SOC-specific T cell activity and on the efficacy of recombinant bispecific antibodies (BsAbs) targeting CD28 and mucin 1 (MUC1). SOC-specific T cells were generated from healthy donor peripheral blood mononuclear cells and assessed for recruitment, activation, and cytotoxicity against low-grade (OVCA433) and high-grade (OVCAR3) SOC cell lines under different treatment conditions.Results\n\nDDR2 inhibition enhanced SOC-specific T cell responses by remodelling the collagen matrix, favouring their recruitment, activation and cytotoxic activity against both low- and high-grade SOC cells. Moreover, combined treatment with DDR2 blockade and CD28xMUC1 BsAbs significantly increased the recruitment of SOC-specific T cells, granzyme B release, caspase-3 activation, and cytokine production.Conclusions\n\nDDR2 blockade mitigates collagen-mediated immune exclusion and enhances the efficacy of CD28xMUC1 BsAb-based immunotherapy in SOC models. These findings provide a mechanistic rationale for further investigation of combined DDR2 targeting and CD28×MUC1 costimulatory strategies to improve ovarian cancer immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology and Biotechnologies \"Charles Darwin\", Sapienza University of Rome, Rome, Italy.",
    "Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.",
    "Institute of Molecular Biology and Pathology (IBPM), CNR, Rome, Italy.",
    "Department of Internal Medicine and Medical Specialties - DIMI, University of Genova, Genova, Italy.",
    "LIFE Institute for Research and Health Care - Santa Lucia IRCCS, Rome, Italy.",
    "Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy.",
    "Research Center for Nanotechnology applied to Engineering, Sapienza University of Rome, Rome, Italy.",
    "Università Cattolica del Sacro Cuore, Rome, Italy.",
    "Unit of Oncological Gynaecology, Department of Woman, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.",
    "Department of Biology and Biotechnologies \"Charles Darwin\", Sapienza University of Rome, Rome, Italy. loretta.tuosto@uniroma1.it.",
    "Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy. loretta.tuosto@uniroma1.it."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Martina Kunkl"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Malatesta"
    },
    {
      "affs": [
        2
      ],
      "name": "Flavia Ottavi"
    },
    {
      "affs": [
        2
      ],
      "name": "Ilenia Masi"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Manolo Sambucci"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Virginia Vigiano Benedetti"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Egle De Stefano",
      "orcid": "0000-0002-5730-2996"
    },
    {
      "affs": [
        0
      ],
      "name": "Martina Leopizzi"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Teresa Fiorillo"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Marco Rossi"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Francesco Mura"
    },
    {
      "affs": [
        5
      ],
      "name": "Anacleto Proietti"
    },
    {
      "affs": [
        7
      ],
      "name": "Enrica Martinelli"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Camilla Nero"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Anna Fagotti"
    },
    {
      "affs": [
        4
      ],
      "name": "Giovanna Borsellino"
    },
    {
      "affs": [
        4
      ],
      "name": "Luca Battistini"
    },
    {
      "affs": [
        2
      ],
      "name": "Valerio Licursi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Francesco Spallotta"
    },
    {
      "affs": [
        2
      ],
      "name": "Laura Rosanò"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Loretta Tuosto"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1xszmb1bg8exq.bib",
  "cited_by": 0,
  "doi": "10.1186/s12916-026-05183-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13721643",
  "id": "1xszmb1bg8exq",
  "issns": [
    "1741-7015"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958545",
  "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"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7204146779",
  "pdf_url": "https://europepmc.org/articles/PMC13721643?pdf=render",
  "pmcid": "PMC13721643",
  "pmid": "42958545",
  "published": "2026-08-24",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/1xszmb1bg8exq.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:45Z",
      "native_id": "MED:42958545",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958545"
    },
    {
      "first_seen": "2026-11-03T12:22:18Z",
      "native_id": "PMC13721643",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12916-026-05183-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Boosting ovarian cancer immunotherapy via discoidin domain receptor 2 blockade and CD28 x mucin 1 bispecific antibodies.",
  "title_text": "Boosting ovarian cancer immunotherapy via discoidin domain receptor 2 blockade and CD28 x mucin 1 bispecific antibodies.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:18Z",
  "url": "https://research.draconitic.com/paper/1xszmb1bg8exq",
  "venue": "BMC medicine",
  "versions": []
}