Attenuation of CD4⁺CD25⁺ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug.

ABSTRACT: CD4⁺CD25⁺ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103⁺KLRG1⁺ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4⁺ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the

SUBMITTER: Kunisada Y 

PROVIDER: S-EPMC5704053 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature