NAD⁺ Metabolism Reprogramming Drives SIRT1-Dependent Deacetylation Inducing PD-L1 Nuclear Localization in Cervical Cancer.

ABSTRACT: Cervical cancer (CC) is a major health threat to women, with immunotherapies targeting the programmed death receptor 1/programmed death ligand 1(PD-1/PD-L1) axis showing promise but encountering resistance in a significant patient population. This resistance has driven a critical quest to uncover the underlying mechanisms. This study uncovers a novel metabolic axis involving the nicotinamide adenine dinucleotide (NAD⁺) salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) and the deacetylase Sirtuin 1 (SIRT1), which regulates PD-L1 expression and nuclear localization in CC. This axis may be a key factor contributing to the resistance observed in immunotherapy. This study reveals that PD-L1 overexpression in cancers is regulated by both transcriptional and post-tr

SUBMITTER: Lu X 

PROVIDER: S-EPMC12005810 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature