Fig. 3: Immune checkpoint blockade and T_reg cell metabolism.

Immune checkpoint molecules such as PD-1, LAG3, and CTLA4 help to stabilize Foxp3 expression by dampening PI3K–AKT signaling and glycolysis. TIM-3 expression is associated with enhanced glycolysis in T_reg cells. Deletion of PD-1 or blockade of CTLA4 signaling is associated with increased PI3K–AKT signaling and glycolysis pathways in T_reg cells, thereby reducing FOXP3 stability; this effect is associated with increased autocrine IFN-γ signaling, which further destabilizes T_reg cell identity.