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首页> 外文期刊>EBioMedicine >Attenuation of CD4 + CD25 + Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug
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Attenuation of CD4 + CD25 + Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug

机译：二甲双胍（一种2型糖尿病药物）在肿瘤微环境中对CD4 + CD25 +调节性T细胞的衰减

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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 na?ve 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 involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity.
机译：CD4 + CD25 + 调节性T细胞（Treg）是预防自身免疫性疾病的重要子集，被认为是抗肿瘤免疫力的负调节剂。我们发现二甲双胍（Met）降低了肿瘤浸润Treg（Ti-Treg），特别是末端分化的CD103 + KLRG1 + 群体，并且还减少了诸如CTLA4和IL-10。 Met通过减少由mTORC1激活引起的叉头盒P3（Foxp3）蛋白来抑制朴素的CD4 + T细胞向诱导型Treg（iTreg）的分化，这是由磷酸化S6（pS6）的升高引起的），是mTORC1的下游分子。雷帕霉素和化合物C（AMP活化蛋白激酶（AMPK）的抑制剂）恢复了iTreg的生成，进一步表明mTORC1和AMPK参与其中。 iTreg的代谢特征，增加的Glut1表达和降低的线粒体膜电位以及Ti-Treg的ROS生成有助于确定Met处理后糖酵解的增强。 Met对Ti-Treg的负面影响可能有助于产生持续的抗肿瘤免疫力。

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