致敏树突细胞及其亚细胞成分对荷胃癌小鼠的免疫治疗作用研究  

Immunotherapy of dendritic cells and its exosomes transfected with mRNA of gastric cancer cells in tumor-carried mice

作　　者：罗治彬[1] 徐采朴[2] 王东[1] 王阁[1] 肖世全[1] 朱高友[3] 房殿春[2] 

机构地区：[1]中国人民解放军第三军医大学大坪医院肿瘤中心,重庆市400042 [2]中国人民解放军第三军医大学西南医院全军消化内科中心,重庆市400038 [3]重庆市垫江高安中心医院,重庆市408306

出　　处：《世界华人消化杂志》2004年第1期9-12,共4页World Chinese Journal of Digestology

摘　　要：目的:了解胃癌组织中DC的功能状态,探讨DC及其所分泌的亚细胞成分exosomes用于防治胃癌的可能性,旨在为胃癌的治疗探索一条新的途径. 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及其所分泌的亚细胞成分exosomes治疗后,小鼠腹水产生率、肿瘤转移率、动物的存活率、瘤体平均质量等指标均明显优于对照组(P<0.01),局部组织中IL-12、IFNγ和IL-18的基因表达水平都明显升高(P<0.01),肿瘤局部CD4+、CD8+ 细胞数量增加(P<0.05),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exoso- mes,能促进胃癌抗原的提呈,并启动和增强局部的抗瘤免疫功能,改善临床症状和宿主的生存质量,对荷胃癌小鼠具有一定的免疫治疗效果.AIM: To unravel the functional status of dendritic cells (DCs) in the tissue of gastric cancer (GC) and precancerous lesions, and to explore the possibility of treating and preventing gastric carcinoma with activated DCs and their exosomes. METHODS: The tumor-bearing mice were treated with DCs sensitized by mRNA of gastric cancer cells and their exosomes, and efficacy of the immunotherapy was observed. RESULTS: The indices such as the production rate of as-cites of mice (75%), the metastasis rate of tumor (25%), the survival rate of animals (75%) and the average mass of tumor (2.04±0.33 g) showed that the condition of the mice treated with DCs was better than that in the control group (p<0.01). The level of gene expression of IL-12, IFNγ and IL-18 in local tumor tissue was significantly risen (P<0.01), the local CD4+ and CD8+cells were increased (P <0.05) and the cytotoxicity of TIL was remarkably enhanced. After immunotherapy of the tumor-bearing mice by using exosomes from DCs transfected with mRNA isolated from murine tumor cells, the indices were as good as those of sensitized DCs. However, DCs transfected with mRNA isolated from mouse tumor cells could effectively inhibit the growth of tumor and ameliorate the symptoms, showing a certain therapeutic efficiency for mice carrying tumor. CONCLUSION: DCs-derived exosomes sensitized by RNA of gastric carcinoma cells can not 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.

关 键 词：致敏树突细胞 亚细胞 胃癌 免疫治疗 

分 类 号：R735.2[医药卫生—肿瘤]