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Oxygenation and A2AR blockade to eliminate hypoxia/HIF-1α-adenosinergic immunosuppressive axis and improve cancer

Katarina Halpin-Veszeleiova1, Stephen M Hatfield1

  • 1New England Inflammation and Tissue Protection Institute, Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, United States.

Current Opinion in Pharmacology
|August 26, 2020
PubMed

Insights

Combining A2AR antagonists with oxygenation therapy shows promise for renal cell carcinoma. This approach targets the hypoxia-adenosinergic pathway to enhance cancer immunotherapies, even in patients resistant to anti-PD-1/PDL-1 treatments.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • The hypoxia-adenosinergic pathway plays a crucial role in tumor immunosuppression.
  • Adenosine receptor A2A (A2AR) antagonists are being investigated for cancer immunotherapy.
  • Clinical responses to A2AR antagonists have been observed in renal cell carcinoma patients, including those refractory to anti-PD-1/PDL-1 therapy.

Purpose of the Study:

  • To evaluate the potential of combining A2AR blockade with systemic oxygenation for cancer treatment.
  • To investigate the synergistic effects of this combination therapy on the hypoxia-adenosinergic axis.

Main Methods:

  • Review of preclinical and clinical data on the hypoxia-adenosinergic pathway.
  • Analysis of the impact of systemic oxygenation on hypoxia-induced immunosuppression.
  • Advocacy for a combined therapeutic strategy.

Main Results:

  • A2AR antagonists show promise in treating renal cell carcinoma.
  • Systemic oxygenation has been shown to counteract the hypoxia-adenosinergic axis.
  • Clinical responses achieved in patients previously treated with anti-PD-1/PDL-1 therapy.

Conclusions:

  • Combining A2AR antagonists with systemic oxygenation may enhance cancer immunotherapy efficacy.
  • This dual approach targets both upstream (hypoxia-HIF-1α) and downstream (adenosine-A2AR) components of the immunosuppressive axis.
  • Maximizing therapeutic benefits of A2AR antagonists and improving tumor susceptibility to treatment is anticipated.

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