Fig. 4. AMPK modulates tumor-infiltrating T cells. AMPK activates CD8+ T cells to secrete IFN-γ/granzyme b and to infiltrate tumor tissues infiltration, which potentiates CTL activity to retard tumor growth. In tumor-infiltrating Treg cells, HMGCR inhibits p38 and GSK3β to elevated PD-1 on Treg cells. Through activating AMPK, HMGCR is repressed, reversing P38/GSK3β function to downregulate PD-1. In methionine-deficient TME, PD-1 expression on CD4+ T cells is increased through elevated ER stress and Xbp1s transcript, but AMPK activation relieves CD4+ T cells from PD1 expression by limiting ER stress-induced Xbp1s transcription. Solid red and blue arrowed lines depict intact and AMPK mediated expressions within tumor infiltrating T cells. The figure is created with BioRender.com.
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