Combinatorial Immunotherapeutic Strategies in Liver Cancer

Background: Immune checkpoint inhibitors combined with antiangiogenic therapy has become the standard of care for advanced hepatocellular carcinoma, albeit with limited therapeutic benefit. Our previous studies demonstrated the immunomodulatory and antitumor effects of polyIC, a synthetic double-stranded RNA. Here, we compared the efficacy of anti-programmed death ligand 1 (?PD-L1) plus polyIC versus ?PD-L1 plus anti-vascular endothelial growth factor (?VEGF) in primary liver tumor models.Conclusion: This preclinical study identifies polyIC as a better enhancer of ?PD-L1 efficacy than ?VEGF in liver cancer, providing a novel strategy for improving immunotherapy outcomes. Further clinical investigation is warranted. We established a primary liver tumor model using hydrodynamic tail vein injection of Ras/Myc oncogenes. Flow cytometry and gene expression analysis were performed to assess immune profiles across treatment groups. Key factors contributing to antitumor efficacy were explored.