姜黄素诱导肿瘤细胞自噬后的自噬体浓缩疫苗抗肿瘤的机制研究

目的研究姜黄素诱导肿瘤细胞自噬后的自噬体浓缩疫苗抗肿瘤的机制。方法细胞自噬通过Western blotting和透射电子显微镜。小鼠骨髓来源的树突状细胞(BMDCs)的成熟表型经常规扫描电子显微镜(SEM)、流式细胞仪(FCM)和透射电子显微镜(TEM)证实。自噬体介导的交叉呈递效率通过羟基荧光素二醋酸盐琥珀酰亚胺脂(CFSE)的分布测定T细胞的增殖。分析自噬体的抗原交叉呈递的机理。结果姜黄素诱导的自噬通过自噬体的电子显微镜以及LC3-Ⅱ的表达所证实。自噬体浓缩疫苗上调表达CD40、CD86和MHCⅡ。经自噬体介导的T细胞激活后,T细胞有明显的扩增同时能杀伤靶细胞。HSP90、HSP70和HMGB1在这种新的疫苗中发挥重要作用。结论这些数据表明以自噬体为基础的疫苗有抗肿瘤疗效独特的特点。这种新的肿瘤疫苗的功效需临床试验的进一步验证。

Mechanism of autophagy concentrated vaccine anti-tumor after curcumin induced tumor cell autophagy

Objective To study the mechanism of autophagy concentrated vaccine anti-tumor after curcumin induced tumor cell autophagy.Methods Autophagy were characterized by Western blotting and transmission electron microscopy.Phenotypic maturation of murine bone marrow derived dendritic cells （BMDCs） was confirmed by conventional scanning electron microscopy （SEM）,flow cytometry （FCM） and functional maturation by transmission electron microscopy （TEM）.The mechanisms of antigen cross-presentation by autophagosome were analyzed.Results Autophagy induced by curcumin was confirmed by electron microscopy and LC3-Ⅱ expression.Autophagy concentrated vaccine up-regulated the expression of CD40,CD86 and MHC Ⅱ.After the autophagy mediated activation of T cells,T cells were amplified and could kill target cells.HSP90,HSP70 and HMGB1 played important roles in the high efficacy of this novel vaccine.Conclusion These data documente autophagosome-based vaccine has the unique characteristics and potent antitumor efficacy.The efficacy of this novel cancer vaccine will be further tested in clinical trials.