辅助性T细胞和细胞毒性T淋巴细胞双表位修饰的树突状细胞肿瘤疫苗治疗胃癌的实验研究  

Immunotherapeutic efficacy of both helper T lymphocytes and cytotoxic T lymphocytes epitopes augmented dendritic cells tumor vaccine on gastric cancer

作　　者：李强[1] 张轶[1] 陈雪华[1] 曹伟新[1] 顾琴龙[1] 朱正纲[1] 刘炳亚[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科上海消化外科研究所

出　　处：《中华胃肠外科杂志》2006年第2期148-151,共4页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金资助项目(30170915)

摘　　要：目的研究辅助性T细胞(Th)表位和细胞毒性T淋巴细胞(CTL)双表位修饰的树突状细胞(DCs)肿瘤疫苗用于胃癌免疫治疗的效果。方法用CTL表位MAGE-341-49和Th表位MAGE-322-36混合多肽冲击DCs,每周刺激脾脏T细胞1次,4周后收集多肽特异性T细胞。流式仪分析T细胞亚群分布,测定CD4+T细胞识别抗原细胞因子分泌及CD8+T细胞杀伤肿瘤细胞效能,观察双表位修饰的DCs肿瘤疫苗治疗胃癌的保护性免疫效应。结果双表位致敏的DCs体外可同时活化CD4+和CD8+T细胞,其中CD4+T细胞识别肿瘤细胞小鼠前胃癌细胞株MFC后分泌大量Th1型细胞因子犤干扰素(IFN)-γ,白介素(IL)-2犦,CD8+T细胞强效杀伤MFC。双表位修饰的DCs肿瘤疫苗小鼠体内免疫治疗获得抵抗后继胃癌细胞MFC的免疫保护能力,并显著高于单一表位(CTL或Th)修饰的DCs疫苗。结论Th和CTL双表位修饰的DCs肿瘤疫苗可同时激活CD4+Th1细胞和CD8+CTL抗肿瘤免疫,有效清除胃癌细胞。Objective To investigate the immunotherapy efficacy of both helper T lymphocytes（Th） and cytotoxic T lymphocytes（CTL） epitopes augmented dendritic cells（DCs） tumor vaccine on gastric cancer. Methods NaYve spleen T cells were stimulated by mixed peptides （a mixture of Th epitope MAGE-341-49 and CTL epitope MAGE-322-36 primed DCs per week in vitro. After 4 cycles of restimulation, peptide specific T cells were harvested and subgroups of which were determined with flowcytometry. Cytokines secreting profiles by CD4^＋ T cells and cytotoxicities of CD8^＋ T cells on tumor cells were assessed. The protective immunity by referred DCs tumor vaccines was also monitored. Results Both Th and CTL epitopes primed DCs could elicit both CD4^＋ T cells and CD8^＋ T cells in vitro, of which CD4^＋ T cells released high amount of Thl type cytokines（IFN-γ IL-2） on recognizing specific antigen, as well as CD8^＋T cells exhibited efficient tumor-killing capacity. The effects induced by DCs pulsed with single epitope （Th or CTL epitope） in vivo were less effective than those induced by DCs pulsed with mixture epitopes. Conclusions Both Th and CTL epitopes augmented DCs tumor vaccine can induce CD4^＋Th1 and CD8^＋ CTL mediated immune responses to eradicate gastric cancer cells.

关 键 词：胃肿瘤 肽类 树突细胞 免疫疗法 

分 类 号：R735.2[医药卫生—肿瘤]