Administration of small molecules or mAbs with the aim to block adenosine-signaling, either by limiting its production or its binding to ARs, has yielded important tumor control in various pre-clinical tumor models. Moreover, simultaneous blockade of adenosine production and receptor binding, achieved by an anti-CD73 mAb co-administered with an A2AR antagonist, for example, have demonstrated it synergy. Given the potent suppression of T cells by adenosine, it comes as no surprise that increases in tumor control and survival conferred by ICB (anti-PD-1 and anti-CTLA-4 mAbs) or ACT, is significantly enhanced by concomitant administration of agents countering the adenosine axis. Synergy of such adenosine axis modulators has further been shown with RT, as well as CTs, schemes known to promote immunogenic cell death (i.e., ATP is released), as well as with some targeted therapies.