T cell exhaustion in poorly immunogenic HCC is partially rescued by checkpoint blockade but suppressed by oncolytic virotherapy.

ABSTRACT: Currently, the benefits of immune checkpoint blockade (ICB) for hepatocellular carcinoma (HCC) are restricted to a subset of patients. We hypothesized that co-treatment with the inflammatory oncolytic virus (OV) vesicular stomatitis virus (VSV-IFNβ) would reprogram the highly immunosuppressive tumor microenvironment (TME) to enhance ICB. However, VSV-IFNβ inhibited the efficacy of ICB. To develop better, mechanism-based immunotherapies for HCC, here, we characterized (1) the baseline T cell response to HCC, (2) its enhancement by ICB, (3) the inhibitory effects of VSV, and (4) the antigenic response of HCC to treatment. We show that a slowly developing anti-tumor CD8⁺ T cell response becomes exhausted, is only initially sensitive to ICB, is outcompeted by a strong anti-viral CD8

SUBMITTER: Sangsuwannukul T 

PROVIDER: S-EPMC12703176 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature