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. 2021 Jan 16;22(2):867. doi: 10.3390/ijms22020867

Figure 2.

Figure 2

Metformin prevents myeloid-derived suppressor cell (MDSC)-mediated T cell exhaustion by downregulating CD39 and CD73 expression. The exposure of MDSCs to metformin activates AMPK and inhibits hypoxia-inducible factor 1-alpha (HIF1α) expression, thereby inhibiting the HIF1α-mediated transcriptional upregulation of CD39 and CD73 and subsequently suppressing cytotoxic CD8+ T lymphocytes (CTCs). This results in a net effect of reduced T cell exhaustion. Blue arrows indicate upregulation/activation, red arrows indicate downregulation/inactivation and red T symbols indicate inhibition.