The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

被引：708

作者：

Allard, Bertrand ^{[1
,2
]}

Longhi, Maria Serena ^{[3
,4
]}

Robson, Simon C. ^{[3
,4
]}

Stagg, John ^{[1
,2
]}

机构：

[1] Ctr Hosp Univ Montreal, Inst Canc Montreal, Ctr Rech, Montreal, PQ, Canada

[2] Univ Montreal, Fac Pharm, Montreal, PQ, Canada

[3] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA

[4] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Transplantat, Boston, MA USA

来源：

IMMUNOLOGICAL REVIEWS | 2017年 / 276卷 / 01期

基金：

美国国家卫生研究院;

关键词：

cancer inflammation; immunity; immunotherapies monocytes/macrophages; T cells; tumor; REGULATORY T-CELLS; ENDOTHELIAL BARRIER FUNCTION; CENTRAL-NERVOUS-SYSTEM; HUMAN BREAST-CANCER; NUCLEOSIDE TRIPHOSPHATE DIPHOSPHOHYDROLASE-1; CHRONIC LYMPHOCYTIC-LEUKEMIA; GROWTH-FACTOR-BETA; MEMORY B-CELLS; EXTRACELLULAR ADENOSINE; ATP RELEASE;

D O I：

10.1111/imr.12528

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：121 / 144

页数：24

共 338 条

[1] Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth [J].