Application possibility of cancer immunotherapy by apoptotic regulation of effector CD8T cells

效应CD8T细胞凋亡调节在癌症免疫治疗中的应用可能性

• 批准号: 20591542
• 负责人: MOGI Akira
• 金额: $ 2.91万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591542/
• 关键词: 癌免疫; アポトーシス; 抗原特異的CD8T細胞; TNFファミリー; Bcl-2ファミリー; 腫瘍抗原特異的CD8T細胞; Fas遺伝子変異マウス; Fas-FasL系; エフェクターCD8T細胞; Fas-FasLシグナル

Observation for time course changes of the tumor antigen specific CD8 T-cells after the administration of EG.7 thymoma cells revealed that the CTL activation was maintained for a long term, so it was suggested that the mechanism of the tumor relapse depend on not the host side but the tumor side. Moreover, in the apoptotic cell death of effector CD8T cells in the tumor immune response, it became clear that the signal transduction through Fas-FasL cascade was important, and it through Bcl-2 was not participating. This result is an event that has not been clarified up to now.In addition, in order to analyze the expression profile of Fas-FasL involving the apoptosis of the tumor antigen specific CD8 T-cells, Fas gene targeting mutated OT-I mouse, FasL gene targeting mutated OT-I mouse, and Bcl-2 gene overexpressed OT-I mouse were constructed. Moreover, Fas gene targeting mutated OT-I cell or a normal OT-I cell was transfused to the normal mouse or the Fas gene mutation mouse intravenously, and the chimera mouse wasconstructed.

在施用EG.7胸腺瘤细胞后，观察肿瘤抗原特异性CD8 T细胞的时间过程变化表明，长期保持CTL激活，因此建议肿瘤复发的机理取决于宿主的机理，不是宿主侧而不是肿瘤侧。此外，在肿瘤免疫反应中效应CD8T细胞的凋亡细胞死亡中，很明显，通过FAS-FASL级联反应的信号转导很重要，并且它通过BCL-2不参与。此结果是迄今尚未澄清的事件。此外，为了分析涉及肿瘤抗原特异性CD8 T细胞凋亡的FAS-FASL的表达曲线，FAS基因靶向突变的OT-I小鼠，FASL基因靶向突变的OT-I小鼠和Bcl-2 Gene exefachers Expercached ot Expercenceed-iT-i tecression tarment ot-ie tarmied。此外，将靶向突变的OT-I细胞或正常OT-I细胞的FAS基因输注正常小鼠或FAS基因突变小鼠，静脉内将嵌合小鼠造成。