ADORA2A and melanoma: Furthermore, adenosine, an important immunosuppressive metabolite generated from ATP by the ectonucleotidases CD73 and CD39 in response to hypoxia and stress (177), has been targeted by blocking the high-affinity A2A adenosine receptor on NK cells, resulting in more potent antitumor activity in mouse models of breast cancer, melanoma and fibrosarcoma (178, 179).