致敏树突细胞及exosome对胃癌的免疫治疗作用研究

A preliminary study of the immunotherapy of dendritic cells transfected with mRNA of gastric cancer cells in carried-tumor mice and its exosomes

目的 :了解胃癌组织中树突细胞 (DC)的功能状态 ,探讨DC及其分泌的亚细胞成分exosomes用于防治胃癌的可能性 ,旨在为胃癌的防治探索新的途径。方法 :利用致敏DC及其所分泌的亚细胞成分exosomes对荷胃癌小鼠进行免疫治疗 ,观察其免疫治疗效果。结果 :荷胃癌小鼠经胃癌细胞RNA致敏的DC及其分泌的亚细胞成分exosomes治疗后 ,小鼠腹水产生率、肿瘤转移率、动物存活率、瘤体平均重量等指标均明显优于对照组 (P <0 0 1) ,局部组织中IL 12、IFN γ和IL 18的基因表达水平都明显升高 (P <0 0 1) ,肿瘤局部CD4 + 、CD8+ 细胞数量增加 (P <0 0 5 ) ,TIL细胞毒活性明显增强。结论 :胃癌RNA致敏的DC及其所分泌的亚细胞成分exosomes,能促进胃癌抗原的提呈 ,并启动和增强机体的抗瘤免疫功能 ,改善临床症状和生存质量 ,对荷胃癌小鼠具有一定的免疫治疗效果。

Objective:Our previous result showed unravel the functional status of DC in the tissue of gastric cancer (GC) and precancerous lesions, and probed into the possibility of preventing solid carcinoma such as GC.Methods:In the experiment of immunotherapy for the tumor-bearing mice,treated by DC sensitized by mRNA of gastric acncer cells.Results:The indices such as the production rate of ascites of mice(75%),the metastasis rate of tumor(25%),the survival rate of animals (75%) and the average weight of trmor(2.04±0.33 g)showed that the condition of the mice treated by DC was better than that in the control group(P<0.01).And the level of gene expression of IL-12, IFNγ and IL-18 in local tumor tissue was signficantly raised (P<0.01) and the amount of local CD4 +?CD8 + cells was increased (P<0.05) and the cytotoxicity of TIL was remarkably enhanced. After immunotherapy of the tumor-bearing mice by using exosomes from DC transfected with mRNA isolated from murine tumor cells, the indices are as good as sensitized DC's.However, DC transfected with mRNA isolated from mouse tumor cells may be effectively control the growth of tumor and ameliorate the symptoms,showing a certain therapeutic efficiency for mice carrying tumor can be realized.Conclusion:DC-derived exosomes sensitized by RNA of gastric carcinoma cells can ont only intensify the local immunologic function of GC but also make a better survival quality of the tumor-bearing host.Being a new type of therapeutic vaccine,exosomes is an important investigative value and a prospect of development.