ADORA2A and neoplasm: Moreover , ADO binding to A2aR activates the cAMP-PKA-cAMP response element-binding protein (CREB) pathway , wherein CREB inhibits nuclear factor kappa B (NF-κB) and nuclear factor of activated T cells (NFAT), resulting in a decrease in the secretion of anti-tumor cytokines such as IL-2, IL-4, IL-5, IL-6, IL-17, IFN-γ, and TNF-α, thereby inhibiting the activation of both CD4+ and CD8+ T cells 47.