{
  "abstract": "Introduction\n\nCancer immunotherapies require accurate preclinical models that recapitulate the complex cellular interactions within the human tumor microenvironment. While patient-derived organoids have emerged as powerful tools for cancer research, standard cultures lack the stromal and immune compartments necessary to evaluate immunotherapeutic mechanisms. This limitation hampers the development of next-generation targeted cytokine therapies.Methods\n\nWe applied a 3D immune-containing colorectal cancer assembloid platform integrating patient-derived organoids, cancer-associated fibroblasts and allogeneic peripheral blood mononuclear cells within a collagen matrix. We characterized cellular responses to interferon-gamma (IFNg) and engineered IFNg receptor agonists targeted to fibroblast activation protein (FAP) through single-cell transcriptomics, immunohistochemistry, cytokine profiling, and functional T-cell migration assays.Results\n\nThe assembloid model successfully recapitulated key features of IFNg signaling, including tissue growth suppression, enhanced chemokine secretion (CXCL10), and CD8⁺ T-cell recruitment. Single-cell transcriptomics revealed that fibroblasts were the most responsive cell population, undergoing a phenotypic transition from myofibroblasts toward antigen-presenting CAFs (apCAFs), characterized by robust upregulation of MHC class II genes. FAP-targeted IFNg molecules exhibited attenuated activity compared to recombinant IFNg, successfully avoiding upregulation of the severe immunosuppressive checkpoint molecule PD-L1.Discussion\n\nThis 3D assembloid model provides a physiologically relevant platform for dissecting complex tumor-immune interactions and optimizing targeted immunotherapies. This approach enables the study of epithelial-stromal-immune crosstalk in cancer and offers a robust preclinical framework for screening and mechanistically validating next-generation targeted cytokine therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Roche Innovation Center Zurich, Roche Pharma Research and Early Development, F. Hoffmann-La Roche , ,",
    "Roche Innovation Center Basel, Roche Pharma Research and Early Development, F. Hoffmann-La Roche , ,",
    "Computational Sciences Center of Excellence, F. Hoffmann-La Roche , ,",
    "Institute of Human Biology (IHB), Roche Pharma Research and Early Development, F. Hoffmann-La Roche , ,",
    "Roche Innovation Center Munich, Roche Pharma Research and Early Development, F. Hoffmann-La Roche , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nina Maenhoudt"
    },
    {
      "affs": [
        0
      ],
      "name": "Mechthild Lütge"
    },
    {
      "affs": [
        1
      ],
      "name": "Melanie Obenloch"
    },
    {
      "affs": [
        0
      ],
      "name": "Aljona Caironi"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Kiratzis"
    },
    {
      "affs": [
        0
      ],
      "name": "Pol Jean-Mairet"
    },
    {
      "affs": [
        2
      ],
      "name": "Samuele Graziano"
    },
    {
      "affs": [
        0
      ],
      "name": "Philipp Fröbel"
    },
    {
      "affs": [
        0
      ],
      "name": "Tamara Hüsser"
    },
    {
      "affs": [
        0
      ],
      "name": "Emilio Yángüez"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Antsiferova"
    },
    {
      "affs": [
        3
      ],
      "name": "Adrian M. Filip"
    },
    {
      "affs": [
        0
      ],
      "name": "Christian Müller"
    },
    {
      "affs": [
        4
      ],
      "name": "Stephane Leclair"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephan Gasser"
    },
    {
      "affs": [
        0
      ],
      "name": "Pablo Umaña"
    },
    {
      "affs": [
        1
      ],
      "name": "Sara Colombetti"
    },
    {
      "affs": [
        0
      ],
      "name": "Floriana Cremasco"
    },
    {
      "affs": [
        0
      ],
      "name": "Samuele Calabro"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4rs10dsk7jm92.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1930651",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717148/?tool=EBI",
  "id": "4rs10dsk7jm92",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13717148",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7222110909",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717148/pdf/?tool=EBI",
  "pmcid": "PMC13717148",
  "pmid": "42959536",
  "published": "2026-10-15",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4rs10dsk7jm92.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13717148",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13717148"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42959536",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959536"
    },
    {
      "first_seen": "2026-11-02T12:21:31Z",
      "native_id": "PMC13717148",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1930651"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Evaluating cytokine-based therapeutics in human 3D in vitro immune-containing assembloids",
  "title_text": "Evaluating cytokine-based therapeutics in human 3D in vitro immune-containing assembloids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:31Z",
  "url": "https://research.draconitic.com/paper/4rs10dsk7jm92",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}