Figure 4.

The effect of hypoxia on anti-GBM immune responses. (a) Under hypoxia, macrophages preferentially show an immunosuppressive M2-like phenotype, rather than an inflammatory M1-like phenotype. Tumor-infiltrating lymphocytes are suppressed in response to activation of HRE genes and mitochondrial dysfunction, and accumulation of lactic acid supports stability and function of regulatory T cells (Tregs), to further suppress inhibit responses. (b) Microglia in the tumor area show an elongated phenotype; these cells are immunosuppressive, with enhanced phagocytosis ability. Oligodendrocyte precursor cells are thought to be a precursor for GBM cells. Connection with neurons also supports GBM progression, whereas PD-L1 expression from neurons is associated with improved prognosis of GBM patients. (c) Hypoxia inhibits functions of natural killer (NK) cells and γδ T cells and promotes dysfunction of NK cell mitochondria.