{
  "abstract": "Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood. Using spatial transcriptomics and multiplex imaging across various human tumors, we found an enrichment of mature dendritic cells (DC) expressing high levels of CCR7 in TLS, prompting us to investigate the role of DC in the formation and maintenance of TLS in solid tumors. To address this, we developed a novel murine model of non-small cell lung cancer (NSCLC) that forms mature TLS, containing B cell follicles with germinal centers and T cell zones with T follicular helper cells (T FH ) and TCF1 + PD-1 + progenitor exhausted CD8 + T cells (Tpex). Here we show that, during the early stages of tumor development, TLS formation relies on IFNγ-driven maturation of the conventional DC type 1 (cDC1) subset, their migration to tumor-draining lymph nodes (tdLN), and recruitment of activated T cells to the tumor site. As tumors progress, TLS maintenance becomes independent of T cell egress from tdLN, coinciding with a significant reduction of cDC1 migration to tdLN. Instead, mature cDC1 accumulate within intratumoral CCR7 ligand-enriched stromal hubs. Notably, timed depletion of cDC1 or disruption of their migration to these stromal hubs after TLS are formed alters TLS maintenance. Importantly, we found that cDC1-mediated antigen presentation to both CD4 + and CD8 + T cells and intact CD40 signaling, is critical for the maintenance of TLS, the preservation of the T FH cell pool, the formation of germinal center and the production of tumor-specific IgG antibodies. These findings underscore the key role of mature cDC1 in establishing and maintaining functional TLS within tumor lesions and highlight the potential for cDC1-targeting therapies as a promising strategy to enhance TLS function and improve anti-tumor immunity in patients with cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Institute for Bioinnovation, “Alexander Fleming” Biomedical Sciences Research Center, Vari, Greece",
    "Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA",
    "Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France",
    "Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy",
    "Department of Biology, Grove City College, Grove City, PA, USA",
    "Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "GIMM, Gulbenkian Institute for Molecular Medicine and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal",
    "Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA",
    "Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA",
    "Global Health and Emerging Pathogens Institute and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Henry D. Janowitz Division of Gastroenterology, Department of Medicine, and Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Genentech, South San Francisco, CA, USA",
    "Paris-Saclay University, Gustave Roussy, INSERM U1015, Villejuif, France"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 68,
  "authors": [
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      "name": "Raphaël Mattiuz",
      "orcid": "0000-0002-3292-1635"
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      "name": "Jesse Boumelha",
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      "name": "Pauline Hamon",
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      "name": "László Halász",
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      "name": "Étienne Humblin",
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      "name": "Raphaël Merand",
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      "name": "Samarth Hegde",
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      "name": "Jean‐Christophe Lone",
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      "name": "Giorgio Ioannou",
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      "name": "Igor Figueiredo"
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      "name": "Alexander Tepper",
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      "name": "Hajer Merarda"
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      "name": "Nadine Serhan",
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      "name": "Maximilian M. Schaefer",
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      "name": "Jinping An",
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      "name": "Ray A. Ohara",
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      "name": "Erika Nemeth",
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      "name": "Simon Goldstein",
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      "name": "Amanda M. Reid",
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      "name": "Alexandra Tabachnikova",
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      "name": "Giulia Maria Piperno",
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      "name": "Maria Tsoumakidou",
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      "name": "Jalal Uddin Ahmed",
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      "name": "Joshua Brody",
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      "orcid": "0000-0002-1641-4094"
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      "name": "Florent Ginhoux",
      "orcid": "0000-0002-2857-7755"
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        15
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      "name": "KENNETH M. M. MURPHY",
      "orcid": "0000-0002-3505-9630"
    },
    {
      "affs": [
        8
      ],
      "name": "Catherine Sautès‐Fridman",
      "orcid": "0000-0003-1735-8722"
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      "affs": [
        8
      ],
      "name": "Wolf H. Fridman",
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      "name": "Brian D. Brown",
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  ],
  "bibtex": "https://research.draconitic.com/paper/35wjgvybg1x9h.bib",
  "cited_by": 40,
  "doi": "10.1126/science.ady1678",
  "fulltext_url": null,
  "id": "35wjgvybg1x9h",
  "issns": [
    "0036-8075",
    "0193-4511",
    "1095-9203"
  ],
  "landing_url": "https://doi.org/10.1126/science.ady1678",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
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  "openalex": "W7168996940",
  "pdf_url": null,
  "pmcid": "PMC11703156",
  "pmid": "42462020",
  "published": "2026-07-16",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/35wjgvybg1x9h.ris",
  "sources": [
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      "native_id": "W7168996940",
      "source": "openalex",
      "url": "https://doi.org/10.1126/science.ady1678"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Dendritic cells control tertiary lymphoid structure development and maintenance in cancer",
  "title_text": "Dendritic cells control tertiary lymphoid structure development and maintenance in cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/35wjgvybg1x9h",
  "venue": "Science",
  "versions": []
}