In the microenvironment of GBM, hypoxia triggers the activation of immunosuppressive pathway, polarization of tumor associated macrophages, and overexpression of immune checkpoint genes, PD-L1 (programmed death-ligand 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) [88]. Here, CTLA4 is linked to glioblastoma.