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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: J Mol Med (Berl). 2014 Aug 15;92(12):1283–1292. doi: 10.1007/s00109-014-1189-3

Fig. 5. Hyperoxic breathing may prevent tumor hypoxia-dependent accumulation of tumor-protecting extracellular adenosine ([Ado]high) in tumor microenvironments.

Fig. 5

Left panel: Tumor hypoxia/HIF-1α-driven and CD39/CD73 ecto-enzyme-generated extracellular [Adenosine]high protects tumors by inhibiting T cells and NK cells through activation of intracellular cAMP-elevating A2A or A2B adenosine receptors (A2AR/A2BR). TME hypoxia may also protect tumors through the stabilization of HIF-1α. At tissue oxygen tension above ∼3%, oxygen-sensing prolyl hydroxylases (PHD) target HIF-1α for degradation, thereby preventing T cell inhibition. Right panel: Hyperoxic breathing 60% [Oxygen]high is expected to weaken the first upstream stage (TME hypoxia) of hypoxia-HIF-1α signaling and thereby inhibit the formation of extracellular [Adenosine]high. This, in turn, may weaken tumor protection and enable T-and NK cells to reject tumors.