ADA and immunodeficiency disease: In NK cells, the signaling of adenosine (ADO) signals via A2AR suppresses their cytokine production and cytotoxicity function.272,273 ADO signaling plays a critical role in immune regulation, as further underscored by the NK cells total dysfunction in individuals presenting with a variant of severe combined immunodeficiency caused when adenosine deaminase (ADA) undergoes a mutation that catalyzes ADO conversion to inosine.262,274,275 Also, the expression of CD38 on tumors, T cells, and NK cells promote the generation of ADO followed by proliferation and suppression of T cell function.