Journal
IMMUNOLOGICAL REVIEWS
Volume 276, Issue 1, Pages 121-144Publisher
WILEY
DOI: 10.1111/imr.12528
Keywords
cancer inflammation; immunity; immunotherapies monocytes/macrophages; T cells; tumor
Categories
Funding
- National Institutes of Health [P01 HL107152, R21 CA164970]
- Ben and Rose Cole Charitable PRIA Foundation
- Leona M. and Harry B. Helmsley Charitable Trust [281574.5069091.0010]
- Canadian Institute of Health Research
- Susan G. Komen Foundation
- Terry Fox Research Institute
- Leukemia and Lymphoma Society of Canada
- Famille Jean-Guy Sabourin Research Chair in Pharmacology
- MITACS Elevate Fellowship
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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.
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