State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
Int J Biol Sci. 2010 Oct 13;6(7):639-48. doi: 10.7150/ijbs.6.639.
The choice of the tumor antigen preparation used for dendritic cell (DC) loading is important for optimizing DC vaccines. In the present study, we compared DCs pulsed with hepatocellular carcinoma (HCC) total RNA or cell lysates for their capacity to activate T cells. We showed here that HCC total RNA pulsed-DCs induced effector T lymphocyte responses which showed higher killing ability to HCC cell lines, as well as higher frequency of IFN-γ producing of CD4+ and CD8+ T cells when compared with lysate pulsed-DCs. Both of RNA and lysate loading did not influence the changes of mature DC phenotype and the capacity of inducing T cell proliferation. However, HCC lysate loading significantly inhibited the production of inflammatory cytokines IL-12p70, IFN-γ and enhanced the secretion of anti-inflammatory cytokines IL-10 of mature DCs. Our results indicated that DCs loaded with HCC RNA are superior to that loaded with lysate in priming anti-HCC CTL response, suggesting that total RNA may be a better choice for DCs-based HCC immunotherapy.
用于树突状细胞 (DC) 加载的肿瘤抗原制剂的选择对于优化 DC 疫苗很重要。在本研究中，我们比较了用肝癌 (HCC) 总 RNA 或细胞裂解物脉冲处理的 DC 激活 T 细胞的能力。我们在这里表明，与用裂解物脉冲处理的 DC 相比，用 HCC 总 RNA 脉冲处理的 DC 诱导的效应 T 淋巴细胞反应显示出更高的杀伤 HCC 细胞系的能力，以及更高频率的 IFN-γ 产生的 CD4+和 CD8+T 细胞。RNA 和裂解物加载都不会影响成熟 DC 表型的变化和诱导 T 细胞增殖的能力。然而，HCC 裂解物加载显著抑制了成熟 DC 中炎症细胞因子 IL-12p70、IFN-γ 的产生，并增强了抗炎细胞因子 IL-10 的分泌。我们的结果表明，负载 HCC RNA 的 DC 在启动抗 HCC CTL 反应方面优于负载裂解物的 DC，这表明总 RNA 可能是基于 DC 的 HCC 免疫治疗的更好选择。
