Targeting A2 adenosine receptors in cancer.
Tumor cells use various ways to evade anti-tumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine-generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate anti-tumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro-angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer. We discuss recent pre-clinical studies and summarize the different mechanisms-of-action of adenosine-targeting drugs. We also review the rationale for combining inhibitors of the adenosine pathway with other anticancer therapies such immune checkpoint inhibitors, tumor vaccines, chemotherapy and adoptive T cell therapy.
Centre de Recherche du, Centre Hospitalier de l'Université de Montréal, et Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada.
David
D
Allard
Centre de Recherche du, Centre Hospitalier de l'Université de Montréal, et Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada.
Martin
M
Turcotte
Centre de Recherche du, Centre Hospitalier de l'Université de Montréal, et Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada.
John
J
Stagg
D015720:5'-Nucleotidase / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001081:Apyrase / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology; D006801:Humans; D007109:Immunity; D016219:Immunotherapy, Adoptive / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009389:Neovascularization, Pathologic; D043683:Receptors, Adenosine A2 / Q000276:immunology / Q000378:metabolism*; D059016:Tumor Microenvironment
D058917:Adenosine A2 Receptor Antagonists; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D061025:Costimulatory and Inhibitory T-Cell Receptors; D043683:Receptors, Adenosine A2; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen