IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer
| Autor: | Jenny Valladeau-Guilemond, Elisa Gobbini, Christophe Sajous, Vincent Ollion, Céline Rodriguez, Olivier Tredan, Margaux Hubert, Isabelle Treilleux, Marc Dalod, Justine Berthet, Bertrand Dubois, Christophe Caux, Janice Kielbassa, Coline Couillault, Anne-Claire Doffin, Thien-Phong Vu Manh, Nathalie Bendriss-Vermare |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Institut de Recherche en Mathématiques, Interactions et Applications (Labex_IRMIA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), SERM, INCA (PLBIO INCa_4508and PLBIO INCa_11155), ANRS, ARC, Ligue contre le Cancer (Régionale Auvergne-Rhône-Alpes et Saône-et-Loire, Comité de la Savoie), and la Région Rhône-Alpes Auvergne (IRICE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Synergie Lyon Cancer [Lyon] |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemokine [SDV]Life Sciences [q-bio] medicine.medical_treatment Immunology Breast Neoplasms Interferon Lambda 03 medical and health sciences 0302 clinical medicine Immune system Breast cancer Interferon Medicine Cytotoxic T cell Humans biology business.industry General Medicine Immunotherapy Dendritic Cells medicine.disease Immunity Innate 3. Good health 030104 developmental biology 030220 oncology & carcinogenesis TLR3 biology.protein Cancer research Female Interferons business Conventional Dendritic Cell medicine.drug |
| Zdroj: | Science Immunology Science Immunology, American Association for the Advancement of Science, 2020, 5 (46), pp.eaav3942. ⟨10.1126/sciimmunol.aav3942⟩ Science Immunology, 2020, 5 (46), pp.eaav3942. ⟨10.1126/sciimmunol.aav3942⟩ |
| ISSN: | 2470-9468 |
| Popis: | International audience; Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through their capacity to produce type III interferon (IFN-λ). By analyzing a large cohort of breast primary tumors and public transcriptomic datasets, we observed specific production of IFN-λ1 by cDC1. In addition, both IFN-λ1 and its receptor were associated with favorable patient outcomes. We show that IFN-III promotes a TH1 microenvironment through increased production of IL-12p70, IFN-γ, and cytotoxic lymphocyte–recruiting chemokines. Last, we showed that engagement of TLR3 is a therapeutic strategy to induce IFN-III production by tumor-associated cDC1. These data provide insight into potential IFN- or cDC1-targeting antitumor therapies. |
| Databáze: | OpenAIRE |
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