Search results for "Nucleotidase"
showing 10 items of 20 documents
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
2015
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical …
Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer
2021
AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based …
CD73 a novel marker for the diagnosis of benign and malignant salivary gland tumors
2019
Background Ecto-5’-nucleotidase (CD73) plays an important role in the development of several types of cancer; however, its prognostic significance in salivary gland tumors remains unknown. The current study was conducted to investigate the expression of CD73 in such tumors. Material and Methods In this retrospective study, immunohistochemical expression of CD73 was evaluated in 25 pleomorphic adenomas, 20 mucoepidermoid carcinomas and 20 adenoid cystic carcinomas using the Envision technique. Labeling indices of CD73 expression were calculated and compared between lesions. Results Immunohistochemical analysis demonstrated that the CD73 expression was significantly higher in salivary gland t…
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death
2011
Abstract Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67+ CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/CD73+ CLL cells generate ADO from ADP in a time- and concentration-dependen…
Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape
2012
It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T …
Fluorescent Probes for Ecto-5′-nucleotidase (CD73)
2020
[Image: see text] Ecto-5′-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes to an immunosuppressive microenvironment. In the present study we designed and synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity and high selectivity based on N(6)-benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure. Fluorescein was attached to the benzyl residue via different linkers resulting in PSB-19416 (14b, K(i) 12.6 nM) and PSB-18332 (14a, K(i) 2.98 nM) as fluorescent high-affinity probes for CD73. These compounds …
Controversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity?
2012
The immune system has important roles in limiting the spread of cancer and shaping the tumor microenvironment. Although the contributions of T helper 17 (Th17) cells (a subtype of CD4(+) T lymphocytes) to autoimmunity and allergy response are well known, their roles in cancer remain ambiguous. Despite adoptive transfer studies indicating that mouse Th17 cells support anticancer immunity, the Th17 cells that naturally infiltrate experimental tumors appear to have a tumor-promoting effect. These contradictory properties can be related to the high degree of plasticity inherent in Th17 cells and their capacity to differentiate into tumoricidal Th1-like cells. Mouse Th17 cells induced by transfo…
Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression
2012
International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to thei…
Tips on ligand immobilization and kinetic study using surface plasmon resonance.
2016
Surface plasmon resonance (SPR) technique offers a robust label-free approach applicable in various investigations including binding affinity, specificity and kinetics of biological macromolecules (e.g., peptides, proteins and nucleotidase) and small molecules. SPR provides extremely important data on the kinetics and affinity of substances examined, through which bio-specific interaction(s) can be established by the analysis of adsorption of analyte onto the immobilized ligand(s) on a sensor-based analytical system. Due to SPR wide applications in biomedical laboratories, the aim of this editorial is to highlight the importance of SPR in affinity kinetics and ligand immobilization.
2.35 CD73-Generated Extracellular Adenosine Creates Microenvironmental Conditions Favoring Growth and Survival of Chronic Lymphocytic Leukemia Cells
2011
Abstract Abstract 621 CD39 (ecto-nucleoside-triphosphate-diphosphohydrolase-1) and CD73 (5'-nucleotidase) are surface enzymes with extracellular catalytic sites. CD39 hydrolyses ATP/ADP to AMP, which is then converted to adenosine (ADO) by CD73. Once ADO is released in the extracellular milieu, it may re-enter the cell or engage different types of purinergic receptors, eliciting potent autocrine and paracrine cytoprotective, anti-inflammatory and immunosuppressive effects. Several lines of evidence suggest that the tumor microenvironment is marked by increased turnover of extracellular nucleotides and nucleosides, as well as by upregulation of ecto-enzymes that dismantle them. These alterat…