The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

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 sta...

Full description

Saved in:
Bibliographic Details
Published in:Immunological reviews 2017-03, Vol.276 (1), p.121-144
Main Authors: Allard, Bertrand, Longhi, Maria Serena, Robson, Simon C., Stagg, John
Format: Article
Language:English
Subjects:
5'-Nucleotidase - immunology
5'-Nucleotidase - metabolism
Adenosine
Animals
Antibodies, Monoclonal - therapeutic use
Antigens, CD - immunology
Antigens, CD - metabolism
Apyrase - immunology
Apyrase - metabolism
Cancer
cancer inflammation
CD73 antigen
Clinical Trials as Topic
Combined Modality Therapy
Drug Evaluation, Preclinical
GPI-Linked Proteins - immunology
GPI-Linked Proteins - metabolism
Humans
Immune checkpoint
Immune response
Immune system
immunity
immunotherapies monocytes/macrophages
Immunotherapy
Immunotherapy - methods
Neoplasms - immunology
Neoplasms - therapy
Rejection
T cells
tumor
Tumor Escape
Tumor Microenvironment
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0105-2896
1600-065X
DOI:10.1111/imr.12528