Astragaloside IV directly targets PPP1R14B to sensitize prostate cancer to anti-PD-1 immunotherapy by remodeling the CX3CL1/CD8+ T cell axis - PubMed
4 hours ago
- #Immunotherapy
- #Prostate Cancer
- #Immune Microenvironment
- Astragaloside IV (AS-IV) targets PPP1R14B, inducing its degradation via ubiquitin-proteasome.
- Degradation of PPP1R14B inhibits Wnt/β-catenin signaling through the AKT/GSK-3β axis and increases mitochondrial ROS.
- This relieves repression of CX3CL1, enhancing recruitment and function of CD8+ T cells.
- In vivo, AS-IV synergizes with anti-PD-1 therapy to suppress prostate cancer growth, dependent on PPP1R14B downregulation.
- The findings propose the AS-IV/PPP1R14B/CX3CL1 axis as a mechanism to overcome immune checkpoint inhibitor resistance.