Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8⁺ T Cells for Enhanced IFNγ Production by Metformin.

ABSTRACT: Metformin (Met), a first-line drug for type 2 diabetes, lowers blood glucose levels by suppressing gluconeogenesis in the liver, presumably through the liver kinase B1-dependent activation of AMP-activated protein kinase (AMPK) after inhibiting respiratory chain complex I. Met is also implicated as a drug to be repurposed for cancers; its mechanism is believed identical to that of gluconeogenesis inhibition. However, AMPK activation requires high Met concentrations at more than 1 mM, which are unachievable in vivo. The immune-mediated antitumor response might be the case in a low dose Met. Thus, we proposed activating or expanding tumor-infiltrating CD8⁺ T cells (CD8TILs) in a mouse model by orally administering Met in free drinking water. Here we showed that Met, at arou

SUBMITTER: Chao R 

PROVIDER: S-EPMC9277540 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature