Emerging Role of Ubiquitination in the Regulation of PD-1/PD-L1 in Cancer Immunotherapy

A growing amount of evidence suggests that ubiquitination and deubiquitination of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) play crucial roles in the regulation of PD-1 and PD-Ll protein stabilization and dynamics. PD-1/PD-L1 is a major coinhibitory checkpoint pathway that modulates immune escape in cancer patients, and its engagement and inhibition has significantly reshaped the landscape of tumor clearance. The abnormal ubiquitination and deubiquitination of PD-1/PD-L1 influence PD-1/PD-Ll-mediated immunosuppression. In this review, we describe the ubiquitination- and deubiquitination-mediated modulation of PD-1/ PD-L1 signaling through a variety of E3 ligases and deubiquitinating enzymes (DUBs). Moreover, we briefly expound on the anticancer potential of some agents that target related E3 gases, which further modulate the ubiquitination of PD-1/ PD-L1 in cancers. Therefore, this review reveals the development of a highly promising therapeutic approach for cancer immunotherapy by targeting PD-1/PD-L1 ubiquitination.

Automated summary

The ubiquitination and deubiquitination of PD-1/PD-L1 play crucial roles in modulating immune escape and tumor clearance, with abnormal ubiquitination influencing immune suppression. Targeting PD-1/PD-L1 ubiquitination may offer a promising therapeutic approach for cancer immunotherapy.