Cordycepin Targets HRD1 to Promote Cancer Cell PD-L1 Ubiquitin-Proteasome Degradation and Increase Antitumor Immunity.

ABSTRACT: Immune checkpoint blockade has become an effective strategy for inhibiting tumor growth, especially immune checkpoint inhibitors that target the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway, which have shown significant effects in tumor immunotherapy. In this study, we found that naturally sourced Cordyceps militaris extract can effectively downregulate the protein expression level of PD-L1 in human colorectal cancer cell lines. Further systematic isolation, purification, and analysis of its active components revealed that cordycepin (COR) is the key active molecule mediating PD-L1 degradation. Mechanistically, COR specifically and selectively targets the ubiquitin E3 ligase HMG-CoA reductase degradation protein 1, thus promoting the degradation of PD-L1 prote

SUBMITTER: Geng X 

PROVIDER: S-EPMC12531455 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature