Can respiratory hyperoxia mitigate adenosine—driven suppression of antitumor immunity?

Presence of hypoxic sub-volumes, extracellular acidosis, and the accumulation of extracellular adenosine (ADO) and lactate are pathophysiological traits in most human solid tumors (1-3). As a consequence of these properties, tumor cells switch to (mal-)adaptive processes and develop aggressive phenotypes and resistance to treatment [e.g., (4-7)]. In a recent review article, a synopsis was presented of the various mechanisms by which tumor hypoxia per se and through indirect actions may contribute to a more aggressive phenotype, to an increased resistance to anticancer therapies, and finally to poor patient outcome (6). In this context it has been outlined that hypoxia-associated ADO-accumulation may be one of the central drivers for the inhibition of anticancer immune response.