The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Issue 1 (March 2017)

• Record Type: Journal Article
• Authors: Allard, Bertrand; Longhi, Maria Serena; Robson, Simon C.; Stagg, John
• Is Part Of: Immunological reviews. Volume 276:Issue 1(2017)
• Page Start: 121
• Page End: 144
• Publication Date: 2017-03
• Subjects: cancer inflammation -- immunity -- immunotherapies monocytes/macrophages -- T cells -- tumor; Immunology -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 616.079
• DOI: 10.1111/imr.12528
• Languages: English
• ISSNs: 0105-2896

Abstract

Summary: 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.