Adenosine binds to four known G-coupled receptors, A1R, A2AR, A2BR, and A3R on immune cells with the majority of immunosuppressive effects thought to be mediated through A2AR and A2BR. A2AR and A2BR elicit immunosuppressive effects on tumor-infiltrating immune cells due to activation of adenylate cyclase, which results in increased intracellular cAMP. This evidence concerns the gene ADORA2A and neoplasm.