Hypoxic tumor cell line lysate-pulsed dendritic cell vaccine exhibits better therapeutic effects on hepatocellular carcinoma

缺氧肿瘤细胞系裂解物脉冲树突状细胞疫苗对肝细胞癌表现出更好的治疗效果

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作者:Long-Bin Jeng ,Fu-Ying Shih ,Yu-Wen Liao ,Woei-Cherng Shyu ,Chiao-Fang Teng

Abstract

Background: Dendritic cell (DC) vaccine is a promising immunotherapy for hepatocellular carcinoma (HCC) via triggering antigen-specific anti-tumor immunity. Hypoxia contributes to higher level and broader spectrum of antigen expression in tumor cells. Methods: This study aims to compare immunological activity and therapeutic efficacy between hypoxic and normoxic HCC cell line lysate-pulsed DC vaccines. Results: The results showed that hypoxic HCC cell line lysate-pulsed DC vaccines exhibited a stronger activity in producing interleukin-12 and promoting T cell proliferation and cytotoxicity in vitro. In HCC mice, hypoxic HCC cell line lysate-pulsed DC vaccines displayed a better efficacy in improving survival time and tumor volume and inducing intratumoral cytotoxic T cell infiltration and activation as well as tumor cell apoptosis. Adenylate kinase 4-derived antigens were important for hypoxic HCC cell line lysate-pulsed DC vaccine-elicited T cell killing. Conclusions: In conclusion, this study demonstrated hypoxic HCC cell line lysate-pulsed DC vaccine as a potential therapeutic strategy for HCC.

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