title: Immunosuppressive activities of adenosine in cancer.
abstract: Multiple immunosuppressive mechanisms impede anti-tumor immunity. Among them, the accumulation of extracellular adenosine is a potent and widespread strategy exploited by tumors to escape immunosurveillance through the activation of purinergic receptors. In the immune system, engagement of A2a and A2b adenosine receptors is a critical regulatory mechanism that protects tissues against excessive immune reactions. In tumors, this pathway is hijacked and hinders anti-tumor immunity, promoting cancer progression. Different groups have highlighted the therapeutic potential of blocking CD73-dependent adenosine-mediated immunosuppression to reinstate anti-tumor immunity. Phase clinical trials evaluating anti-CD73 antibodies and A2a receptor antagonists in cancer patients are currently ongoing. We here review the recent literature on the immunosuppressive effects of extracellular adenosine and discuss the development of adenosine inhibitors.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, 900 Rue Saint-Denis, H2X0A9 Montréal, QC, Canada; Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Beavis
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Pathology, University of Melbourne, Parkville, Australia.
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Darcy
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, 900 Rue Saint-Denis, H2X0A9 Montréal, QC, Canada; Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, Canada. Electronic address: john.stagg@umontreal.ca.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D043705:Receptor, Adenosine A2A / Q000276:immunology; D043704:Receptor, Adenosine A2B / Q000276:immunology; D011983:Receptors, Purinergic / Q000276:immunology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D011983:Receptors, Purinergic; D015720:5'-Nucleotidase; D000241:Adenosine