Fig. 6

Hypoxia induces differentiation of T-cells to Tregs. T cells directly promote the expression of Foxp3 through the HIF signaling pathway. T cells promote the expression of TGF-β through HIF signaling, inhibit the key enzyme PHD2 for HIF-1α degradation, and indirectly promote the expression of Foxp3. Tumor cells promote the expression of TGF-β through the HIF signaling pathway, act on the receptors on the surface of T cells, activate the downstream SMAD signaling pathway, and promote the expression of Foxp3.Tumor cells promote the expression of PD-L1 on the cell surface through the HIF signaling pathway, bind PD-1 on the surface of T cells, inhibit the downstream AKT and mTOR pathways, and promote the expression of Foxp3