Downregulation of PD-L1 expression by Wnt pathway inhibition to enhance PD-1 blockade efficacy in hepatocellular carcinoma.

ABSTRACT:

Background

Immunotherapy targeting the programmed death-ligand 1 (PD-L1) pathway is a standard treatment for advanced hepatocellular carcinoma (HCC). The Wnt signaling pathway, often upregulated in HCC, contributes to an immunosuppressive tumor microenvironment. This study investigated the impact of Wnt pathway inhibition on PD-L1 expression in HCC and evaluated the potential therapeutic benefit of combining Wnt pathway inhibition with PD-L1 blockade.

Methods

The effects of Wnt pathway inhibitors XAV939 and IWR-1 on PD-L1 expression were examined in human HCC cell lines HuH7 and Hep3B. Beta-catenin overexpression and knockdown experiments confirmed these findings. For in vivo efficacy, the BNL 1ME A.7R.1 mouse HCC cell line was orthotopically implanted in mice, which were su

SUBMITTER: Shao YY 

PROVIDER: S-EPMC11987266 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature