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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591542
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Gunma University
• Principal Investigator: MOGI Akira Gunma University, 大学院・医学系研究科, 助教 (10323362)
• Co-Investigator(Kenkyū-buntansha): ASAO Takayuki 群馬大学, 大学院・医学系研究科, 准教授 (40212469) ; MOCHIKI Erito 群馬大学, 医学部, 講師 (80312883)
• Project Period (FY): 2008 – 2010
• Keywords: 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

Research Abstract

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.