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Caspase-3 deficiency inhibits the development and anti-tumor response of bone marrow-derived dendritic cells

Year: 2025

Type: article

Abstract: This study investigated the impact of Caspase-3 gene deletion on bone marrow-derived dendritic cells (BMDCs) and their anti-tumor functions. BMDCs were generated in vitro using GM-CSF and IL-4 from Caspase-3 knockout (Casp3-KO) and heterozygous (Heter) mouse progenitors. Caspase-3 ablation reduced dendritic cell numbers in vivo and hindered BMDC generation in vitro. Casp3-KO BMDCs exhibited impaired maturation, characterized by diminished dendritic arborization and reduced expression of surface markers (CD80, CD86, CXCR4, MHCI, MHCII). Migration assays revealed Caspase-3 deficiency impaired BMDC motility both in vitro and in vivo. Critically, Casp3-KO BMDCs showed compromised capabilities in phagocytosing tumor antigens and activating naïve T cells. In vivo tumorigenicity assays demonstrated that Caspase-3 deletion undermined the ability of BMDCs to suppress tumor growth. This attenuation correlated with reduced infiltration of CD4 + and CD8 + T lymphocytes at primary tumor sites and draining lymph nodes. These findings provide novel insights into the essential role of Caspase-3 in BMDC development, maturation, migration, antigen presentation, and anti-tumor efficacy. The data suggests Caspase-3 is crucial for the optimal function of dendritic cells in initiating anti-tumor immune responses, potentially informing the development of more effective cancer immunotherapies.

Source: Discover Oncology

DOI: 10.1007/s12672-025-04118-2