Adenosine A2A and A2B receptors (A2AR/A2BR)

The Adenosine A2A and A2B receptors (A2AR and A2BR) are G protein-coupled receptors that serve as critical metabolic checkpoints in the adenosinergic immunosuppressive pathway [1]. In the tumor microenvironment, extracellular ATP released from stressed or dying cells is converted into adenosine by the sequential action of ecto-enzymes CD39 and CD73 [2]. Adenosine then binds to A2AR and A2BR on the surface of effector T cells and antigen-presenting cells (APCs), triggering an increase in intracellular cyclic AMP (cAMP) [3]. This signaling cascade suppresses the activation, proliferation, and cytokine production of anti-tumor immune cells while promoting the activity of regulatory T cells and myeloid-derived suppressor cells [4]. Consequently, tumors exploit this axis to evade immune surveillance. Therapeutic strategies involve using small-molecule antagonists to block these receptors, thereby restoring anti-tumor immunity and enhancing the efficacy of other immunotherapies like PD-1 inhibitors [5, 6]. (Sources: [1] Leone & Emens, JITC 2018; [2] Antonioli et al., Nat Rev Cancer 2013; [3] Sitkovsky et al., Br J Pharmacol 2004; [4] Vijayan et al., Nat Rev Cancer 2017; [5] Corvus Pharmaceuticals; [6] Arcus Biosciences).

Other names

ADORA2AADORA2BAdenosine A2 receptor familyA2A receptorA2B receptorAdenosine receptor A2aAdenosine receptor A2b

Antagonism of A2A and A2B receptors to block adenosine-mediated increases in intracellular cAMP, thereby preventing the suppression of effector T cells and antigen-presenting cells in the tumor microenvironment.