DUSP6 ablation restores CAR T-cell fitness impaired by tumor CD58 loss through invigoration of AP-1 signaling - PubMed
6 hours ago
- #CAR T-cell therapy
- #AP-1 signaling
- #DUSP6
- Primary resistance to CAR T-cell therapies is a significant limitation.
- Loss of CD58 in tumors leads to impaired CAR T-cell activation and cytotoxicity.
- AP-1-mediated activation is attenuated in CAR T cells affected by tumor CD58 loss.
- AP-1 attenuation causes mitochondrial dysfunction and intrinsic apoptosis in CAR T cells.
- DUSP6 blockade restores AP-1 signaling, enhancing CAR T-cell fitness and cytotoxicity.
- Transcriptomic profiles show upregulated T-cell activation and metabolic pathways in DUSP6-ablated CAR T cells.
- DUSP6 downregulation correlates with better responses to T-cell-based immunotherapy in patients.
- DUSP6 ablation is a promising strategy to improve CAR T-cell efficacy.