FBXO9 promotes anti-tumor immunity via degradation of PD-L1 in pancreatic cancer.

ABSTRACT: Immune checkpoint blockade therapy, particularly those targeting programmed death 1/programmed cell death ligand 1 (PD-1/PD-L1), has been extensively employed to treat various human cancers, significantly improving clinical outcomes. Increasing evidence reveals that the therapeutic efficacy of PD-1/PD-L1 inhibitors depends on the abundance of PD-L1 on cancer cells and tumor-associated stromal cells. Here, we demonstrated that F-box protein 9 (FBXO9) is a novel regulator of PD-L1. We found that increased expression of FBXO9 suppresses tumor growth and promotes cytotoxic T cell activation in vivo. Mechanistically, FBXO9 directly binds to PD-L1 protein and enhances its degradation via ubiquitination, thereby impeding PD-L1 maturation and tumor immune evasion. Meanwhile, the expression

SUBMITTER: Cao T 

PROVIDER: S-EPMC12867838 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature