Immunological mechanisms of the antitumor effects of supplemental oxygenation

Antitumor T cells either avoid or are inhibited in hypoxic and extracellular adenosine-rich tumor microenvironments (TMEs) by A2A adenosine receptors. This may limit further advances in cancer immunotherapy. There is a need for readily available and safe treatments that weaken the hypoxia-A2-adenosinergic immunosuppression in the TME. Recently, we reported that respiratory hyperoxia decreases intratumoral hypoxia and concentrations of extracellular adenosine. We show that it also reverses the hypoxia-adenosinergic immunosuppression in the TME. This, in turn, stimulates (i) enhanced intratumoral infiltration and reduced inhibition of endogenously developed or adoptively transfered tumor-reactive CD8 T cells,…

• BF
  Bankhead-Coley Foundation
• NI
  National Institutes of Health

  Awards: U19 AI 091693, R01 CA 112561, R21 AT 002788, R01 CA 111985
• NC
  National Cancer Institute

  Award: 5PO1CA109094-03
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: AI096396-01 3, DK091190, CA168628, DK068575, DK079307, HL109002