CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression

Jin, Dachuan; Fan, Jia; Wang, Long; Thompson, Linda F.; Liu, Aijie; Daniel, Benjamin J.; Shin, Tahiro; Curiel, Tyler J.; Zhang, Bin

doi:10.1158/0008-5472.can-09-3109

Cited by 374 publications

(410 citation statements)

References 51 publications

Supporting

Mentioning

384

Contrasting

Unclassified

Order By: Relevance

“…Ecto-5′-NT/CD73 expression in cancer cells has been also linked with drug resistance [26,59] and immune escape [44,60]. Moreover, researchers have already targeted ecto-5′-NT/ CD73 in an attempt to develop promising therapies, for instance, ecto-5′-NT/CD73 inhibitors have shown antiproliferative effects in bladder cancer cell lines and gliomas [61,62], and decrease in ovarian cancer progression [63]. The treatment of mice with anti-CD73 antibody inhibited breast tumor growth and metastasis [20], and the use of RNA interference of ecto-5′-NT/CD73 inhibited cell growth and invasion in human breast cancer cells [25].…”

Section: Discussionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

View full text Add to dashboard Cite

According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5′-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5′-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5′-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5′-nucleotidase/ CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5′-nucleotidase/ CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…Extracellular adenosine generated by CD73 on tumor cells negatively regulated both activation and effector phases of the antitumor T-cell response. However, it promoted T-cell apoptosis by binding A2aAR on T cells (27). Stagg et al reported that CD73-derived adenosine enhanced tumor-cell migration in vitro and metastasis in vivo through the activation of A2bAR.…”

Section: Discussionmentioning

confidence: 99%

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

View full text Add to dashboard Cite

SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

show abstract

“…in [201,202]). The enzyme has a broad tissue distribution, and it is expressed by subpopulations of human T and B lymphocytes and also by a considerable variety of tumor cells [203]. Catalytic activity varies considerably between individual tissues [204].…”

Section: Ecto-5′-nucleotidasementioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

View full text Add to dashboard Cite

Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

show abstract

CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression

Cited by 374 publications

References 51 publications

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Cellular function and molecular structure of ecto-nucleotidases

Contact Info

Product

Resources

About