Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy

Article Article scientifique Article Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy eng 2023-11-23 author Ghasemi Ali Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Martinez-Usatorre Amaia 0000-0002-3416-1529 Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Li Luqing Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Hicham Mehdi 0000-0002-9979-4757 Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. 402634 Département de pathologie et immunologie (PATIM) author Guichard Alan 0000-0001-8623-9570 Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Marcone Rachel Agora Cancer Research Center, Lausanne, Switzerland.,Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. author Fournier Nadine 0000-0002-9347-7929 Agora Cancer Research Center, Lausanne, Switzerland.,Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. 982766 Services communs de la faculté de médecine (SCMU) author Torchia Bruno Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Martinez Bedoya Darel 0000-0002-1603-5801 Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland. 932040 Département de médecine (DEMED) author Davanture Suzel Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland. 982947 Département de médecine (DEMED) author Fernández-Vaquero Mirian Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. author Fan Chaofan Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. author Janzen Jakob Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. author Mohammadzadeh Yahya Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Genolet Raphael Ludwig Institute for Cancer Research, Lausanne, Switzerland.,Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Mansouri Nahal Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.,Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. author Wenes Mathias 0000-0001-8478-8592 Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland. 983986 Département de médecine (DEMED) author Migliorini Denis 0000-0003-0151-3222 Agora Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland.,Department of Oncology, Geneva University Hospital (HUG), Geneva, Switzerland. 838158 Département de médecine (DEMED) author Heikenwalder Mathias 0000-0002-3135-2274 Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.,The M3 Research Center, Eberhard Karls University, Tübingen, Germany.,Cluster of Excellence iFIT (EXC 2180), Eberhard Karls University, Tübingen, Germany. author De Palma Michele 0000-0001-9128-5459 Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland. michele.depalma@epfl.ch.,Agora Cancer Research Center, Lausanne, Switzerland. michele.depalma@epfl.ch.,Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. michele.depalma@epfl.ch. 10.1038/s43018-023-00668-y 37996514 2662-1347 https://www.nature.com/articles/s43018-023-00668-y Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-? signaling but did not require CD8<sup>+</sup>T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies. Dewey 616 European Commission Extracellular Vesicle-Internalizing Receptors (EVIRs) for Cancer ImmunoGeneTherapy 725051 EVOLVE EU H2020 European Commission Cellular and molecular mechanisms of metabolic immune activation triggering non-alcoholic steatohepatitis (NASH) and HCC 683000 HepatoMetaboPath EU H2020 Swiss Cancer League KLS-4505-08-2018 Swiss National Science Foundation Role of extracellular vesicles in chemotherapy-induced metastasis 188868 CH Projects EVIR Therapeutics Fondation pour la lutte contre le cancer Helmholtz Future topic Inflammation and Immunology Rainer-Hoenig foundation Swiss Institute for Experimental Cancer Research—ISREC Foundation Anita and Werner Damm-Etienne Foundation Association Frédéric Fellay 56 Département de médecine 221 false 1310 Tumeurs cérébrales 1016 0a6434c9-7972-44ea-8708-82e501660dc7 Biomedical Data Science Facility 1462 Contrôle métabolique de l'immunité 1072 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228014 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228161 Nature cancer f748f333-693b-4945-a0a9-4a4bfb769112 Article (Published version) Public Ghasemi Nature Cancer 2023.pdf 17760671 application/pdf CC BY-4.0 ef00e451789e0797664767bbb04c3eb560b23b297654b6b14c3dff7c61ce50c8 e507c360-a944-411a-982c-6583cfdfab72 Appendix Public 43018_2023_668_MOESM1_ESM.pdf 6980335 application/pdf Supplementary Figs. 1–7 and Supplementary Table 1 9c0031fbc4768750a4f52e8ad771207a0200cadb53fb686850f67ee42bcb68ee b57f0e27-3a26-4d7b-b00d-d41b1c4e978a Appendix Public 43018_2023_668_MOESM2_ESM.pdf 11408225 application/pdf Reporting summary 7a6ae0ef18e59c54a8ff59db6e6d00dee617fb4e3fe4041a7527ab8522145915 064b2760-c586-470e-906b-af9835877d8d Supplemental data Public 43018_2023_668_MOESM3_ESM.xlsx 15007 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Statistical Source Data Fig. 1 2e4c61be1b2bb37be80c9f1aa6679c1d7f7f1ea2d48bab48485cf60627c0f339 1d9fa395-11dc-4ed4-a534-e0870e307094 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