Activated ATF6α is a hepatic tumour driver restricting immunosurveillance - PubMed
3 months ago
- #ATF6α
- #Immunosurveillance
- #Hepatocellular Carcinoma
- Activated ATF6α is identified as a hepatic tumour driver that restricts immunosurveillance in hepatocellular carcinoma (HCC).
- ATF6α activation in human HCC correlates with aggressive tumour phenotypes, reduced patient survival, and local immunosuppression.
- In mice, hepatocyte-specific ATF6α activation leads to progressive hepatitis, ER stress, immunosuppression, and hepatocyte proliferation.
- ATF6α increases glycolysis and directly represses the gluconeogenic enzyme FBP1, contributing to metabolic dysregulation.
- Restoring FBP1 expression can mitigate pathologies associated with ATF6α activation.
- Prolonged ATF6α activation triggers hepatocarcinogenesis and immune exhaustion, which can be reversed by immune checkpoint blockade (ICB).
- Patients with HCC responding well to immunotherapy show increased ATF6α activation.
- Targeting ATF6α through various methods reduces HCC in preclinical models, suggesting it as a therapeutic target.