BCL2 inhibition stimulates dendritic cell function for improved anticancer immunotherapy - Centre de recherche des Cordeliers Access content directly
Journal Articles Genes and Immunity Year : 2024

BCL2 inhibition stimulates dendritic cell function for improved anticancer immunotherapy

Abstract

Recently we developed a dendritic cell (DC) genotype-phenotype screening platform that is based on CRISPR/Cas9-mediated gene editing of immortalized DC precursors. Whole genome screening for gain-of-function phenotypes led to the identification of BCL2 as a DC-specific immune checkpoint. Genetic or pharmacological inhibition of BCL2 similarly enhanced the antigen presentation capacity of conventional type-1 dendritic cells (cDC1) and mediated T cell-dependent anticancer immunity. The therapeutic anticancer efficacy of the BCL2 inhibitor venetoclax in mice was further increased when combined with a PD-1-targeted immune checkpoint inhibitor. In sum, we delineated a novel strategy of dual checkpoint blockade for cancer immunotherapy in which improvement of DC antigen presentation and avoidance of T cell exhaustion can be advantageously combined.
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Wednesday, July 24, 2024
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Wednesday, July 24, 2024
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hal-04601362 , version 1 (04-06-2024)

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Peng Liu, Liwei Zhao, Guido Kroemer, Oliver Kepp. BCL2 inhibition stimulates dendritic cell function for improved anticancer immunotherapy. Genes and Immunity, 2024, ⟨10.1038/s41435-024-00256-9⟩. ⟨hal-04601362⟩
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