Proteasome-guided haem signalling axis contributes to T cell exhaustion - PubMed
5 hours ago
- #CAR-T therapy
- #Proteasome activity
- #T cell exhaustion
- Exhausted CD8+ T cells show increased proteasome activity due to depolarized mitochondria accumulation.
- Mitochondrial protein degradation releases regulatory haem, disrupting BACH2-mediated transcription and worsening T cell exhaustion.
- Inhibiting nuclear import of regulatory haem prevents BACH2 degradation, enhancing anti-tumour efficacy of T cells.
- Human CD19+ CAR-T cell efficacy in B cell acute lymphoblastic leukaemia negatively correlates with proteasome gene signature.
- Manufacturing CAR-T cells with proteasome inhibitor bortezomib prevents exhaustion and improves therapeutic outcomes.
- The study identifies a proteasome-guided haem signalling axis as a key regulator of T cell exhaustion.