Murine (121–127) and human (128–132) T cells express all four ARs, and levels of A2AR (122, 124–127, 129), A2BR (126, 127, 130), and A3R (127, 131) increase upon T cell activation. However, the biology of T cells is primarily affected by the predominantly expressed A2AR (122, 123, 128, 132). Of note, similarly to CD39 and CD73, A2AR, and A2BR are upregulated due to hypoxia-induced HIF1α (133) transcriptional activity. Moreover, mRNA levels of both A2AR and A2BR are upregulated in T cells specifically upon provision of anergic stimulus (134). Validating these findings, adoptively transferred tumor-specific T cells isolated from tumors contained twice the A2AR mRNA levels than counterpart T cells isolated from spleens of tumor-bearing mice (135). Since triggering of the different ARs initiates diverse and even antagonistic signaling pathways, the net cellular effects of adenosine are determined by the relative surface expression of its receptors. It is clear, however, that treatment of human (136, 137) or murine (38, 126, 138, 139) T cells with adenosine or adenosine analogs induces A2AR- (38, 126, 137–139) as well as A2BR- (38, 136) mediated intracellular cAMP build-up.