PTEN deficiency impairs MHC-I-mediated tumour immunity via NRF2-dependent autophagy in microsatellite stable colorectal cancer - PubMed
3 hours ago
- #MHC-I degradation
- #PTEN deficiency
- #NRF2 autophagy
- PTEN deficiency in microsatellite stable colorectal cancer (MSS CRC) leads to impaired MHC-I-mediated tumour immunity, contributing to immune checkpoint blockade (ICB) resistance.
- Mechanistically, PTEN loss causes KEAP1 degradation, NRF2 hyperactivation, and upregulation of selective autophagy, which drives lysosomal degradation of MHC-I, preventing CD8+ T-cell recognition.
- Pharmacological inhibition of NRF2 with ML385 restores MHC-I levels and sensitizes PTEN-deficient tumours to anti-PD-1 therapy, suggesting a therapeutic strategy to enhance immunotherapy efficacy in MSS CRC.