While lymphocytes in both C-GBM and NC-GBM showed impaired responses to inflammatory cytokines (Figure 7) (arguing for exhaustion), lymphocytes in C-GBM tumors demonstrated moderate responses to inflammatory cytokines, particularly through CREB, suggesting that these lymphocytes may retain tonic signaling, preventing apoptosis, and may respond to immune-targeted therapies. Here, CREB1 is linked to glioblastoma.