Blocking PCSK9 suppresses hepatocellular carcinoma immune escape by decreasing FLI1-mediated SPP1 and PD-L1 expression.

ABSTRACT:

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly identified immunosuppressive regulator, but its mechanism of suppressing antitumor immunity remains ambiguous. This study aims to uncover the underlying mechanism by which PCSK9 promotes hepatocellular carcinoma (HCC) immune escape and to explore potential intervention strategies.

Methods

Co-culture assay assessed the cytotoxicity of CD8⁺ T cells against PCSK9-knockout HCC cells. Hepa1-6, H22, and HepG2 cells were used to establish HCC mouse models. Tumor microenvironment changes were evaluated using flow cytometry and single-cell RNA sequencing. Additionally, we developed a CRISPR adenine base editing (ABE) base editor and screened small molecule inhibitors for PCSK9 inhibition in HCC tre

SUBMITTER: Hu C 

PROVIDER: S-EPMC12666174 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature