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

Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono

研究成果: Article

23 引用 (Scopus)

抜粋

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 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.

元の言語English
ページ(範囲)154-164
ページ数11
ジャーナルEBioMedicine
25
DOI
出版物ステータスPublished - 2017 11

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

フィンガープリント Attenuation of CD4<sup>+</sup> CD25<sup>+</sup> Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Kunisada, Y., Eikawa, S., Tomonobu, N., Domae, S., Uehara, T., Hori, S., Furusawa, Y., Hase, K., Sasaki, A., & Udono, H. (2017). Attenuation of CD4+ CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug. EBioMedicine, 25, 154-164. https://doi.org/10.1016/j.ebiom.2017.10.009