Cancer-Associated Fibroblasts Promote Tumor Immunosuppression in Hepatocellular Carcinoma via the NNMT-ANGPTL4 Axis - PubMed
5 hours ago
- #Hepatocellular carcinoma
- #Cancer-associated fibroblasts
- #NNMT-ANGPTL4 axis
- Cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC) promote immunosuppression via the NNMT-ANGPTL4 axis.
- NNMT in CAFs binds EZH2, reduces H3K27me3 at the ANGPTL4 promoter, increasing ANGPTL4 secretion.
- ANGPTL4 activates aerobic glycolysis in HCC cells via GLUT1, raising H3K18la levels, which upregulates PD-L1 expression, leading to immune evasion.
- CAF-derived ANGPTL4 also promotes angiogenesis in HCC.
- Targeting the NNMT-ANGPTL4 axis restored CD8+ T-cell activity and synergized with anti-PD-L1 therapy in models.