Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis - PubMed
19 hours ago
- #Immunotherapy Resistance
- #mTORC1 Signaling
- #Tumor Microenvironment
- Inflammatory cytokines in the tumor microenvironment hijack mTORC1 signaling even under nutrient insufficiency.
- ZBTB5, phosphorylated at S127, degrades NPRL2 in the GATOR1 complex to reactivate mTORC1 and boost tumor amino acid uptake.
- Increased tumor amino acid uptake worsens nutrient restriction and death of CD8+ T cells, promoting immunotherapy resistance.
- Blocking ZBTB5-pS127 alleviates resistance to immune checkpoint inhibitors, suggesting a potential therapeutic strategy.