WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.

Methods

We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay were used to examine the function and mechanism of WWOX in the tumor immune response.

Results

WWOX was the most upregulated CFS-related gene in HCC patients responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in humanized orthotopic HCC mouse model. Macrophage infiltrati

SUBMITTER: Liu S 

PROVIDER: S-EPMC11552608 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature