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

IF 6.4 1区医学 Q1 ONCOLOGY

British Journal of Cancer Pub Date : 2025-03-07 DOI:10.1038/s41416-025-02975-w

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

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Abstract

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. This study aims to compare immunological activity and therapeutic efficacy between hypoxic and normoxic HCC cell line lysate-pulsed DC vaccines. 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. In conclusion, this study demonstrated hypoxic HCC cell line lysate-pulsed DC vaccine as a potential therapeutic strategy for HCC.

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低氧肿瘤细胞系裂解液脉冲树突状细胞疫苗对肝癌有较好的治疗效果。

背景：树突状细胞（DC）疫苗通过触发抗原特异性抗肿瘤免疫，是一种很有前景的肝细胞癌（HCC）免疫疗法。缺氧使肿瘤细胞中抗原表达水平更高，表达谱更广。方法：比较缺氧和常氧肝癌细胞裂解液脉冲DC疫苗的免疫活性和治疗效果。结果：缺氧HCC细胞系裂解液脉冲DC疫苗在体外产生白细胞介素-12、促进T细胞增殖和细胞毒性方面表现出较强的活性。在肝癌小鼠中，低氧肝癌细胞系裂解液脉冲DC疫苗在提高存活时间和肿瘤体积、诱导瘤内细胞毒性T细胞浸润活化和肿瘤细胞凋亡方面表现出较好的效果。腺苷酸激酶4衍生抗原对于缺氧HCC细胞系裂解液脉冲DC疫苗诱导的T细胞杀伤是重要的。结论：总之，本研究证明缺氧HCC细胞系裂解物脉冲DC疫苗是HCC的潜在治疗策略。

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来源期刊

British Journal of Cancer 医学-肿瘤学

CiteScore

15.10

自引率

1.10%

发文量

383

审稿时长

6 months

期刊介绍： The British Journal of Cancer is one of the most-cited general cancer journals, publishing significant advances in translational and clinical cancer research.It also publishes high-quality reviews and thought-provoking comment on all aspects of cancer prevention,diagnosis and treatment.