In the LGG cohort, ICOS showed robust positive correlation with allograft rejection in CGGA301 (NES = 2.719, FDR < 0.001) (Figure 4A) followed by other hallmark gene sets, including interferon-gamma response (NES = 2.630, FDR < 0.001), epithelial–mesenchymal transition (NES = 2.546, FDR < 0.001), inflammatory response (NES = 2.545, FDR < 0.001), and IL6-JAK-STAT3 signaling (NES = 2.442, FDR < 0.001), which strongly pointed to the participation of ICOS in the glioma-related immune response. This evidence concerns the gene ICOS and central nervous system cancer.