TY  - JOUR
AU  - Ghasemi, Ali
AU  - Martinez-Usatorre, Amaia
AU  - Li, Luqing
AU  - Hicham, Mehdi
AU  - Guichard, Alan
AU  - Marcone, Rachel
AU  - Fournier, Nadine
AU  - Torchia, Bruno
AU  - Martinez Bedoya, Darel
AU  - Davanture, Suzel
AU  - Fernández-Vaquero, Mirian
AU  - Fan, Chaofan
AU  - Janzen, Jakob
AU  - Mohammadzadeh, Yahya
AU  - Genolet, Raphael
AU  - Mansouri, Nahal
AU  - Wenes, Mathias
AU  - Migliorini, Denis
AU  - Heikenwälder, Mathias
AU  - De Palma, Michele
TI  - Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
JO  - Nature cancer
VL  - 5
IS  - 2
SN  - 2662-1347
CY  - London
PB  - Nature Research
M1  - DKFZ-2023-02449
SP  - 240-261
PY  - 2024
N1  - 2024 Feb;5(2):240-261
AB  - 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-γ 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37996514
DO  - DOI:10.1038/s43018-023-00668-y
UR  - https://inrepo02.dkfz.de/record/285587
ER  -