{
  "abstract": "BACKGROUNDTGF-β drives fibroblast activation in cancer and is a resistance biomarker to PD-1/PD-L1 blockade.METHODSFocusing on the tumor stroma, we characterized the impact of neoadjuvant treatment with bintrafusp alfa (BA), a dual PD-L1 and TGF-β inhibitor, in a window-of-opportunity study with 6 patients with head and neck squamous cell carcinoma (HNSCC). Tumor biopsies before treatment and 3 weeks after therapy were analyzed using scRNA-seq, imaging, and spatial transcriptomics.RESULTSAfter treatment, we observed significantly decreased levels of activated LRRC15+ cancer-associated fibroblasts (CAFs), remodeled stromal architecture with reduced collagen I and XII content, and increased CD8+ T cell infiltration in immune-excluded tumors. These changes were independently confirmed in an additional neoadjuvant BA-treated cohort of 6 patients with HNSCC. The drastic CAF and stromal compartment reduction observed indicated a fibroblast depletion rather than a fibroblast polarization shift.CONCLUSIONWhile our final clinical cohort does not allow assessment of the treatment effect, this study demonstrated that targeting TGF-β in patients can disrupt the tumor stroma within a short time frame. Further trials and novel biomarkers are now needed to select patients who could benefit.TRIAL REGISTRATIONClinicalTrials.gov NCT04428047.FUNDINGMerck KGaA, ARC Emerging Leaders in Oncology, ANR-10-IDEX-0001-02 PSL, Centre d'Investigation Clinique IGR-Curie 1428, Site de Recherche Intégrée sur le Cancer (INCa-DGOS-Inserm-ITMO cancer_18000), French Government \"Investissements d'Avenir\" program, France 2030 program, Fondation pour la Recherche Médicale, Marie Skłodowska-Curie grant agreement 847718, Cooperative Research and Development Agreement with EMD Serono, and NIH (ZIA BC 010666).",
  "abstract_shown": true,
  "affiliations": [
    "Equipe Leader Fondation ARC, INSERM U932, Immunity and Cancer, Institut Curie, PSL University, Paris, France.",
    "Surgical Oncology Department, Institut Curie, Paris, France.",
    "Department of Biostatistics, Centre Lacassagne, Nice, France.",
    "Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.",
    "Department of Pathology and",
    "Single Cell Initiative, Institut Curie, Paris, France.",
    "Department of Drug Development and Innovation (D3i), Institut Curie, Paris & Saint-Cloud, INSERM U900 Research Unit, Paris-Saclay University, Orsay, France.",
    "Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France.",
    "GenoSplice, Paris, France.",
    "Inserm U1331, Institut Curie, PSL University, Paris, France.",
    "Institut Hospitalo Universitaire PRISM, National PRecISion Medicine Center in Oncology, Gustave Roussy, Paris, France.",
    "Department of Genetics, Institut Curie, Paris, France.",
    "Unicancer, Le Kremlin-Bicêtre, France.",
    "Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, and",
    "Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 37,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Caroline Hoffmann"
    },
    {
      "affs": [
        0
      ],
      "name": "Jan-Timon Werle"
    },
    {
      "affs": [
        0
      ],
      "name": "Philémon Sirven"
    },
    {
      "affs": [
        0
      ],
      "name": "Mamy Andrianteranagna"
    },
    {
      "affs": [
        2
      ],
      "name": "Jocelyn Gal"
    },
    {
      "affs": [
        3
      ],
      "name": "Wiem Lassoued"
    },
    {
      "affs": [
        4
      ],
      "name": "Jerzy Klijanienko"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeremy Mesple"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Demaille"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdenour Abbas"
    },
    {
      "affs": [
        0
      ],
      "name": "Valentine Gauthier"
    },
    {
      "affs": [
        5
      ],
      "name": "Kyra J.E. Borgman"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle Puisieux"
    },
    {
      "affs": [
        0
      ],
      "name": "Serena Janho dit Hreich"
    },
    {
      "affs": [
        1
      ],
      "name": "Olivier Choussy"
    },
    {
      "affs": [
        6
      ],
      "name": "Gregoire Marret"
    },
    {
      "affs": [
        5
      ],
      "name": "Sonia Lameiras"
    },
    {
      "affs": [
        1
      ],
      "name": "Nathalie Badois"
    },
    {
      "affs": [
        1
      ],
      "name": "Antoine Dubray-Vautrin"
    },
    {
      "affs": [
        7
      ],
      "name": "Gilles Dolivet"
    },
    {
      "affs": [
        7
      ],
      "name": "Lionnel Geoffrois"
    },
    {
      "affs": [
        4
      ],
      "name": "Renaud Leclère"
    },
    {
      "affs": [
        8
      ],
      "name": "Wail Zeitouni"
    },
    {
      "affs": [
        8
      ],
      "name": "Noemie Robil"
    },
    {
      "affs": [
        9
      ],
      "name": "Jane Merlevede"
    },
    {
      "affs": [
        9
      ],
      "name": "Altynbek Zhubanchaliyev"
    },
    {
      "affs": [
        6,
        10
      ],
      "name": "Maud Kamal"
    },
    {
      "affs": [
        11
      ],
      "name": "Ivan Bieche"
    },
    {
      "affs": [
        12
      ],
      "name": "Laure Monard"
    },
    {
      "affs": [
        12
      ],
      "name": "Clotilde Simon"
    },
    {
      "affs": [
        0
      ],
      "name": "Delphine Louis"
    },
    {
      "affs": [
        13
      ],
      "name": "Clint T. Allen",
      "orcid": "0000-0001-6586-5804"
    },
    {
      "affs": [
        14
      ],
      "name": "Arun Rajan"
    },
    {
      "affs": [
        3
      ],
      "name": "James L. Gulley",
      "orcid": "0000-0002-6569-2912"
    },
    {
      "affs": [
        0
      ],
      "name": "Maude Guillot-Delost"
    },
    {
      "affs": [
        6
      ],
      "name": "Christophe Le Tourneau",
      "orcid": "0000-0001-9772-4686"
    },
    {
      "affs": [
        0
      ],
      "name": "Hélène Salmon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9tk7t38jj1sce.bib",
  "cited_by": 0,
  "doi": "10.1172/jci198718",
  "fulltext_url": "https://europepmc.org/articles/PMC13722384",
  "id": "9tk7t38jj1sce",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://europepmc.org/article/MED/42969228",
  "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",
      "Clinical Research and Public Health"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7225048513",
  "pdf_url": "https://europepmc.org/articles/PMC13722384?pdf=render",
  "pmcid": "PMC13722384",
  "pmid": "42969228",
  "published": "2026-11-02",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/9tk7t38jj1sce.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42969228",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42969228"
    },
    {
      "first_seen": "2026-11-04T12:22:00Z",
      "native_id": "PMC13722384",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci198718"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Neoadjuvant PD-L1/TGF-β blockade can rapidly disrupt the tumor stroma in head and neck cancer patients.",
  "title_text": "Neoadjuvant PD-L1/TGF-β blockade can rapidly disrupt the tumor stroma in head and neck cancer patients.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:12Z",
  "url": "https://research.draconitic.com/paper/9tk7t38jj1sce",
  "venue": "The Journal of clinical investigation",
  "versions": []
}