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Targeting Adenosine Receptor Signaling in Cancer Immunotherapy

by Kevin Sek 1,2, Christina Mølck 3, Gregory D. Stewart 4, Lev Kats 1,2, Phillip K. Darcy 1,2,3,5,*,† and Paul A. Beavis 1,2,*,†
1
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3000, Australia
2
Sir Peter MacCallum Department of Oncology, The University of Melbourne, 3010 Parkville, Australia
3
Department of Pathology, University of Melbourne, Parkville 3010, Australia
4
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville 3052, Australia
5
Department of Immunology, Monash University, Clayton 3052, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(12), 3837; https://doi.org/10.3390/ijms19123837
Received: 30 October 2018 / Revised: 27 November 2018 / Accepted: 27 November 2018 / Published: 2 December 2018
(This article belongs to the Special Issue Purinergic Signalling in Cancer and Inflammation)
The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of ‘checkpoint blockade’ and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient’s own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function. The production of extracellular adenosine is mediated by the cell surface ectoenzymes CD73, CD39, and CD38 and therapeutic agents have been developed to target these as well as the downstream adenosine receptors (A1R, A2AR, A2BR, A3R) to enhance anti-tumor immune responses. This review will discuss the role of adenosine and adenosine receptor signaling in tumor and immune cells with a focus on their cell-specific function and their potential as targets in cancer immunotherapy. View Full-Text
Keywords: Adenosine; Adenosine receptors; immune cells; tumor cells; cancer immunotherapy Adenosine; Adenosine receptors; immune cells; tumor cells; cancer immunotherapy
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Sek, K.; Mølck, C.; Stewart, G.D.; Kats, L.; Darcy, P.K.; Beavis, P.A. Targeting Adenosine Receptor Signaling in Cancer Immunotherapy. Int. J. Mol. Sci. 2018, 19, 3837.

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