Regulation of function and antitumor effect of regulatory T cells in the tumor microenvironment by metformine, a type 2 diabetes drug

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Okayama University
• Principal Investigator: Kunisada Yuki 岡山大学, 大学病院, 医員 (10779416)
• Research Collaborator: UDONO Heiichiro ; EIKAWA Shingo
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: Treg / メトホルミン / 代謝

Outline of Final Research Achievements

We have already demonstrated that the type 2 diabetes drug metformin has antitumor activity via immune cells. In this study, we analyzed the effect of metformin on immunoregulatory regulatory T cells (Tregs), which are said to contribute to tumor growth.
In the mouse tumor transplantation model, we observed that administration of metformin induced Treg apoptosis and suppressed Treg function in only tumor local sites. In addition, we demonstrated that the metabolism of Treg, which metabolism is dominant in fatty acid oxidation, is predominantly changed from fatty acid oxidation to glycolytic metabolism at the time of differentiation / induction from non-Treg cells to Treg.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

メトホルミンは世界中で使用されている糖尿病薬であり、安全性や実用性が高い。また、その費用も安価である。さらに、全身のTregには影響を与えず、腫瘍局所のみに作用することを明らかとしており、自己免疫疾患の副作用が生じにくいえ、非常に革新的である。腫瘍内Tregのみを制御する薬剤の報告は未だになかったため、本研究での結果は学術的にも社会的にも非常に高いといえる。