Figure 1.

Hypoxia inhibits the immune response by inhibiting immune cells, recruiting immunosuppressive cells, regulating CAFs, promoting tumor cell growth, and mediating immune escape. (A) Anoxic metabolites, lactic acid, and adenosine inhibit T cell effector function and proliferation by blocking the mTOR pathway and interacting with the A2A receptor on the T cell surface. Hypoxia promotes T cell apoptosis and directly inhibits T cell proliferation and differentiation. Hypoxia upregulates IL-10, VEGF, and other cytokines through HIF-1α and inhibits the differentiation and maturation of DCs, leading to the inhibition of T cell function. Moreover, hypoxia-induced high levels of HIF-1α and BNIP3 promote programmed cell death in tumor cells captured by DC. In addition, hypoxia inhibits NK cell function by activating the PI3K/mTOR signaling pathway. (B) Hypoxia induced the mRNA expression of TGF-β, VEGF, IL-6, IL-10, and PD-L1 and promoted CAF participation in the recruitment of MDSCs, Tregs, and type 2 TAMs to maintain the immunosuppressive state of the microenvironment, promoting tumor cells to evade immune surveillance. (C) Hypoxia upregulates the expression of MMP adam10 and induces the immune escape of tumor cells.