title: Adenosine and adenosine receptors in the immunopathogenesis and treatment of cancer.
abstract: Tumor cells overcome anti-tumor responses in part through immunosuppressive mechanisms. There are several immune modulatory mechanisms. Among them, adenosine is an important factor which is generated by both cancer and immune cells in tumor microenvironment to suppress anti-tumor responses. Two cell surface expressed molecules including CD73 and CD39 catalyze the generation of adenosine from adenosine triphosphate (ATP). The generation of adenosine can be enhanced under metabolic stress like tumor hypoxic conditions. Adenosine exerts its immune regulatory functions through four different adenosine receptors (ARs) including A1, A2A, A2B, and A3 which are expressed on various immune cells. Several studies have indicated the overexpression of adenosine generating enzymes and ARs in various cancers which was correlated with tumor progression. Since the signaling of ARs enhances tumor progression, their manipulation can be promising therapeutic approach in cancer therapy. Accordingly, several agonists and antagonists against ARs have been designed for cancer therapy. In this review, we will try to clarify the role of different ARs in the immunopathogenesis, as well as their role in the treatment of cancer.
authors.affiliation: Student Research Committee, Department of Immunology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.|Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Kazemi
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Raoofi Mohseni
authors.affiliation: Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden.|Department of Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hojjat-Farsangi
authors.affiliation: Faculty of Medicine, Department of Physiology, Ilam University of Medical Sciences, Ilam, Iran.
authors.forename: Enayat
authors.initials: E
authors.lastname: Anvari
authors.affiliation: Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ghalamfarsa
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Faculty of Medicine, Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Mohammadi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.|Faculty of Medicine, Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Farhad
authors.identifier: http://orcid.org/0000-0002-4641-882X
authors.initials: F
authors.lastname: Jadidi-Niaragh
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis*; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D043683:Receptors, Adenosine A2 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D043683:Receptors, Adenosine A2; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine
keywords: adenosine; adenosine receptors; cancer; immunopathogenesis; treatment