Reversion of exhausted T cells in tumor microenvironment

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670237
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Okayama University
• Principal Investigator: Udono Heiichiro 岡山大学, 医歯(薬)学総合研究科, 教授 (50260659)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 免疫疲弊 / CD8T細胞 / 腫瘍微小環境 / メトホルミン

Outline of Final Research Achievements

Elevation of glycolysis in CD8 tumor infiltration lymphocyte (CD8TIL) was found by metformin (Met) administration. Also, mature CD8T cells differentiated from naive CD8T cells by in vitro TCR stimulation revealed enhanced glycolysis as well as oxidative phosphorylation by Met-treatment. Intestinal micro flora was not altered by Met. Significant reduction of Treg in tumors was also observed by Met. Inducible Treg (iTreg) differentiated from naive CD4T cells by TCR stimulation and TGFbeta was reduced in number and suppressive function by Met-treatment. Furthermore, reduction of MDSC in number, especially, G-MDSC rather than M-MDSC, was prominent in tumor tissue by Met. Also, increase of M1/M2 macrophage ration was observed by Met. It is clear that Met-administration dramatically changes tumor microenvironment towards favorable state for anti-tumor immunity.

Free Research Field

免疫学