title: The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.
abstract: Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are newly developing interventions that modify the patient's immune system to fight cancer, by either directly stimulating rejection-type processes or blocking suppressive pathways. Extracellular adenosine generated by the ectonucleotidases CD39 and CD73 is a newly recognized "immune checkpoint mediator" that interferes with anti-tumor immune responses. In this review, we focus on CD39 and CD73 ectoenzymes and encompass aspects of the biochemistry of these molecules as well as detailing the distribution and function on immune cells. Effects of CD39 and CD73 inhibition in preclinical and clinical studies are discussed. Finally, we provide insights into potential clinical application of adenosinergic and other purinergic-targeting therapies and forecast how these might develop in combination with other anti-cancer modalities.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal et Institut du Cancer de Montréal, Montréal, QC, Canada.|Faculté de Pharmacie, Université de Montréal, Montréal, QC, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.affiliation: Divisions of Gastroenterology and Transplantation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Longhi
authors.affiliation: Divisions of Gastroenterology and Transplantation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal et Institut du Cancer de Montréal, Montréal, QC, Canada.|Faculté de Pharmacie, Université de Montréal, Montréal, QC, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001081:Apyrase / Q000276:immunology / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen
keywords: T cells; cancer inflammation; immunity; immunotherapies monocytes/macrophages; tumor