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Rethinking the adenosine-A2AR checkpoint: implications for enhancing anti-tumor immunotherapy.

Authors
  • Helms, Rachel S1
  • Powell, Jonathan D2
  • 1 The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, 1650 Orleans Street, CRB-I Rm443, Baltimore, MD, 21231, USA.
  • 2 The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, 1650 Orleans Street, CRB-I Rm443, Baltimore, MD, 21231, USA. Electronic address: [email protected]
Type
Published Article
Journal
Current opinion in pharmacology
Publication Date
Aug 08, 2020
Volume
53
Pages
77–83
Identifiers
DOI: 10.1016/j.coph.2020.07.003
PMID: 32781414
Source
Medline
Language
English
License
Unknown

Abstract

Adenosine signaling through A2AR serves as a negative regulator of the immune system. Unique to this suppressive pathway is its ability to impact numerous stromal and immune cells. Additionally, tumors exhibit elevated concentrations of adenosine further advancing the pathway's potential as a powerful target for activating anti-tumor immunity. The promise of this therapeutic strategy has been repeatedly demonstrated in mice, but has so far only yielded limited success in the clinic. Nonetheless, it is notable that many of these observed clinical responses have been in individuals resistant to prior immunotherapy. These observations suggest this pathway is indeed involved in tumor immune evasion. Thus, identifying the disparities between the translational and clinical implementation of this therapy becomes necessary. To this end, this review will revisit how and where adenosine-A2AR signaling regulates the immune system and anti-tumor immunity so as to reveal opportunities for improving the translational success of this immunotherapy. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

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