Metformin enhances the antitumor activity of CD8+ T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway

Zhen Zhang, Feng Li, Yonggui Tian, Ling Cao, Qun Gao, Chaoqi Zhang, Kai Zhang, Chunyi Shen, Yu Ping, Nomathamsanqa Resegofetse Maimela, Liping Wang, Bin Zhang, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Metformin has been studied for its anticancer effects by regulating T cell functions. However, the mechanisms through which metformin stimulates the differentiation of memory T cells remain unclear.We found that the frequencies of memory stem and central memory T cells increased for both in peripheral and tumor-infiltrating CD8+ T cells in metformin-treated lung cancer patients compared with those not taking the medication. An in vitro assay showed that metformin promoted the formation of memory CD8+ T cells and enhanced their antiapoptotic abilities. In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells. In the CAR-T cell therapy model, metformin also exhibited cytotoxicity-promoting effects that led to decreased tumor growth. Metformin could reprogram the differentiation of CD8+ T cells, which may benefit the clinical therapy of cancer patients by facilitating long-lasting cytotoxic functions.

Original languageEnglish (US)
Pages (from-to)2575-2588
Number of pages14
JournalJournal of Immunology
Volume204
Issue number9
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhang, Z., Li, F., Tian, Y., Cao, L., Gao, Q., Zhang, C., Zhang, K., Shen, C., Ping, Y., Maimela, N. R., Wang, L., Zhang, B., & Zhang, Y. (2020). Metformin enhances the antitumor activity of CD8+ T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway. Journal of Immunology, 204(9), 2575-2588. https://doi.org/10.4049/jimmunol.1901213