A rational advancement of ICI therapy is co-targeting multiple immune checkpoints, with clinical trials initiated to test the following combinations in GBM: anti-CTLA4 and/or anti-PD-1 with TMZ in newly diagnosed GBM (NCT02311920), anti-CTLA-4 and anti-PD-L1 in recurrent GBM (NCT02794883), anti-LAG-3 and anti-PD-1 in recurrent GBM (NCT02658981), anti-IDO with anti-CTLA4 or anti-PD-1 in GBM (NCT02327078). This evidence concerns the gene CD274 and glioblastoma.