High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma

Zhang, Bin; Cheng, Bo; Li, Fengsheng; Ding, Jianhua; Feng, Yingying; Zhuo, Guangzuan; Wei, Huafeng; Zhao, Ke

doi:10.1007/s13277-015-3683-9

Cited by 33 publications

(26 citation statements)

References 22 publications

(46 reference statements)

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“…High‐tissue CD39 mRNA levels correlated with better long‐term survival after tumor resection . A subsequent investigation conducted in the setting of human rectal carcinoma revealed heightened CD39 expression both in primary tumors and metastases, although it was proposed that the combination of both CD39 and CD73, rather than CD39 alone, could provide a better prognostic value …”

Section: Cd39 In Human Cancersmentioning

confidence: 99%

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

Allard

Longhi

Robson

et al. 2017

Immunological Reviews

700

610

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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 by 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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Section: Cd39 In Human Cancersmentioning

confidence: 99%

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

Allard

Longhi

Robson

et al. 2017

Immunological Reviews

700

610

View full text Add to dashboard Cite

show abstract

“…High expression of the ecto-nucleotidase CD39 occurs in malignant epithelial cells of human rectal adenocarcinoma (Zhang et al, 2015). P2X7R activation mediated inflammatory responses and suppressed colitis associated cancer development.…”

Section: Gut Cancermentioning

confidence: 99%

Purinergic drug targets for gastrointestinal disorders

Burnstock

Christofi

2017

Current Opinion in Pharmacology

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Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuron, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuronal death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway. The latter pathway also mediates morphine-induced constipation and gut inflammation that may differ from opioid-induced constipation (OIC). P2X7R antagonists are protective in inflammatory bowel disease (IBD) models, where as AZD9056 is questionable in CD, but is potentially beneficial for chronic abdominal pain. Drug targets under investigation for IBD, IBS and motility disorders include P2X7R, P2X3R, P2Y2R, A2A/A2BAR, enzymes and transporters.

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“…In tumors, all these partners are present: (i) ATP is mainly released by dying cells and infiltrated immune cells, 12,13 (ii) CD39 and CD73 are expressed by numerous primary tumor cells 43,44 and by some infiltrating immunosuppressive cells [45][46][47][48] and (iii) adenosine receptor 2A is expressed by immune-infiltrating cells. 41 Furthermore, an accumulation of extracellular adenosine in tumor microenvironment and the subsequent purinergic signaling are involved in the regulation of immune cell functions.…”

Section: Introductionmentioning

confidence: 99%

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

et al. 2016

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(2016) The ectoATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSFmacrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27, OncoImmunology, 5:7, e1178025, DOI: 10.1080/2162402X.2016 Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14 C CD163 C TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14 high CD163 high CD39 high macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163 C macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.

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High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma

Cited by 33 publications

References 22 publications

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

Purinergic drug targets for gastrointestinal disorders

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

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