ADORA2A and melanoma: In the regulation of Th cell differentiation, inosine exerts bidirectional regulation on Th1 differentiation through the adenosine A2A receptor (A2AR), and its effects are environment-dependent: In the presence of exogenous IFN-γ and IL-12 secreted by dendritic cells, guanosine promotes Th1 differentiation by binding to the A2AR on the surface of T cells, and significantly enhances the anticancer activity of Th1 cells in various tumors such as melanoma, bladder cancer, and CRC (He et al., 2017).