Tomonobu Nahoko, Eikawa Shingo, Udono Heiichiro
Nihon Rinsho. 2017 Feb;75(2):323-328.
The rate of cancer incidence and mortality of Type 2 diabetes patients who were taking metformin seem to be decreased, comparing with those taking other drugs. We recently pro- vided compelling evidence showing that the effect might be mediated by immune system, thus, the reversion of exhausted tumor infiltrating CD8T lymphocytes (CD8TIL). Glycolysis is essential in CD8T cell function. However, the metabolism of CD8TIL is locked in a state of oxidative phosphorylation (OxPhos) dominant over glycolysis because of interaction between immune checkpoints and their ligands, and because of extremely low concentration of glu- cose in tumor microenvironment. Metformin increases the glycolysis efficiency, resulting in the conversion of CD8TIL to more active effector memory to fight against cancers.
与服用其他药物的2型糖尿病患者相比，服用二甲双胍的患者癌症发病率和死亡率似乎有所降低。我们最近提供了有力证据表明，这种效果可能是由免疫系统介导的，因此，耗尽的肿瘤浸润性CD8T淋巴细胞（CD8TIL）得以恢复。糖酵解对CD8T细胞功能至关重要。然而，由于免疫检查点与其配体之间的相互作用，以及肿瘤微环境中葡萄糖浓度极低，CD8TIL的代谢处于以氧化磷酸化（OxPhos）为主导而非糖酵解的状态。二甲双胍可提高糖酵解效率，从而使CD8TIL转变为更活跃的效应记忆细胞以对抗癌症。
