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. Overall design: 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.

背景：免疫检查点抑制剂（immune checkpoint inhibitors）联合抗血管生成治疗（antiangiogenic therapy）已成为晚期肝细胞癌（hepatocellular carcinoma）的标准治疗方案，但临床获益有限。本团队既往研究证实了合成双链RNA聚肌苷酸-聚胞苷酸（polyIC）的免疫调节与抗肿瘤效应。本研究对比了抗程序性死亡配体1（anti-PD-L1）联合polyIC，与anti-PD-L1联合抗血管内皮生长因子（anti-VEGF）在原发性肝肿瘤模型中的疗效。结论：本临床前研究证实，在肝癌中polyIC相较于anti-VEGF可更有效地增强anti-PD-L1的治疗效果，为改善免疫治疗结局提供了全新策略，有待进一步开展临床研究。总体实验设计：本研究通过流体动力尾静脉注射法将Ras/Myc癌基因导入宿主，构建原发性肝肿瘤模型。采用流式细胞术与基因表达分析，评估各治疗组的免疫特征，并探究影响抗肿瘤疗效的关键因素。