Ghasemi, AliMartinez-Usatorre, AmaiaLi, LuqingHicham, MehdiGuichard, Alan Nicolas ThierryMarcone, RachelFournier, NadineTorchia, BrunoBedoya, Darel MartinezDavanture, SuzelFernandez-Vaquero, MirianFan, ChaofanJanzen, JakobMohammadzadeh, YahyaGenolet, RaphaelMansouri, NahalWenes, MathiasMigliorini, DenisHeikenwalder, MathiasDe Palma, Michele2024-02-192024-02-192024-02-192023-11-2310.1038/s43018-023-00668-yhttps://infoscience.epfl.ch/handle/20.500.14299/204308WOS:001107175200001Dendritic 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-gamma signaling but did not require CD8+ 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.|De Palma and colleagues develop a dendritic cell therapy based on dendritic cell progenitors engineered to produce IL-12 and FLT3L and show antigen-agnostic reduction of tumor burden that can be exploited for combination therapy in glioma.Life Sciences & BiomedicineCd8 T-CellsInterleukin-12SuppressionExpressionResponsesLymphocytesActivationGenerationImmunityTherapytext::journal::journal article::research article