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https://www.readbyqxmd.com/read/28617999/adenosine-an-endogenous-mediator-in-the-pathogenesis-of-gynecological-cancer
#1
REVIEW
Amirhossein Bahreyni, Seyed Sattar Samani, Elnaz Ghorbani, Farzad Rahmani, Reza Khayami, Younes Toroghian, Reihane Behnam-Rassouli, Majid Khazaei, Mikhail Ryzhikov, Mohammad Reza Parizadeh, Malihe Hasanzadeh, Amir Avan, Seyed Mahdi Hassanian
Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28603527/intratumoral-foxp3-helios-regulatory-t-cells-upregulating-immunosuppressive-molecules-are-expanded-in-human-colorectal-cancer
#2
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Bassam R Ali, Eyad Elkord
Regulatory T cells (Tregs) can be antitumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC, but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28578124/influence-of-photodynamic-therapy-on-peripheral-immune-cell-populations-and-cytokine-concentrations-in-head-and-neck-cancer
#3
M N Theodoraki, K Lorenz, R Lotfi, D Fürst, C Tsamadou, S Jaekle, J Mytilineos, C Brunner, J Theodorakis, T K Hoffmann, S Laban, P J Schuler
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. However, the systemic impact on peripheral immune cells has not been described so far. METHODS: HNSCC patients (n=9) were treated with PDT in a palliative setting. All patients had previously undergone several oncologic treatment regimens...
May 31, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28574843/characterization-of-tumor-associated-t-lymphocyte-subsets-and-immune-checkpoint-molecules-in-head-and-neck-squamous-cell-carcinoma
#4
Axel Lechner, Hans Schlößer, Sacha I Rothschild, Martin Thelen, Sabrina Reuter, Peter Zentis, Alexander Shimabukuro-Vornhagen, Sebastian Theurich, Kerstin Wennhold, Maria Garcia-Marquez, Lars Tharun, Alexander Quaas, Astrid Schauss, Jörg Isensee, Tim Hucho, Christian Huebbers, Michael von Bergwelt-Baildon, Dirk Beutner
The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA-/CCR7-)...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554875/cd39-limits-p2x7-receptor-inflammatory-signaling-and-attenuates-sepsis-induced-liver-injury
#5
Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R Figliuolo, Thiago F de Avelar Almeida, Patrícia T Santana, Suellen D S Oliveira, Claudia L M Silva, Linda Feldbrügge, Eva Csizmadia, Richard D Minshall, Maria Serena Longhi, Yan Wu, Simon C Robson, Robson Coutinho-Silva
BACKGROUND & AIMS: The severity of sepsis can be linked to excessive inflammatory responses resulting in hepatic injury with progressive cholestasis. Monocyte/macrophages have been linked to the pathogenesis of cholestasis, cellular injury, and liver failure. P2X7 receptor activation by extracellular ATP (eATP) exacerbates inflammation by augmenting cytokine production; while CD39 scavenges eATP to generate adenosine, thereby limiting P2X7 activation and resulting in A2A receptor stimulation...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28547381/purinergic-signalling-links-mechanical-breath-profile-and-alveolar-mechanics-with-the-pro-inflammatory-innate-immune-response-causing-ventilation-induced-lung-injury
#6
REVIEW
Djo Hasan, Paul Blankman, Gary F Nieman
Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells...
May 26, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#7
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#8
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#9
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28529533/low-expression-of-cd39-and-cd73-genes-in-centenarians-compared-with-octogenarians
#10
Almudena Crooke, Juan Martínez-Henández, Joaquín Martínez-López, Alfonso Cruz-Jentoft, Fernando Huete-Toral, Jesús Pintor
Ageing involves a progressive decline of the body's regulatory systems including immune system. Adenosine regulates immune function by interaction with its receptors, mainly adenosine A2A receptor, present on the surface of immune cells. Furthermore, cellular response to this nucleoside is highly dependent on its extracellular concentration that is regulated by ecto-enzymes such as CD39 and CD73. Therefore, the aim of this study was to investigate the effect of age on adenosine A2A receptor, CD39 and CD73 gene expression...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#11
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28509416/the-importance-of-cd39-cd43-cd81-and-cd95-expression-for-differentiating-b-cell-lymphoma-by-flow-cytometry
#12
Chandra Chiappin Cardoso, Mariangeles Auat, Iris Mattos Santos-Pirath, Renata Cristina Messores Rudolf-Oliveira, Jessica Pires da Silva, Bárbara Gil Lange, Danielle Siegel, Ana Carolina Rabello de Moraes, Joanita Angela Gonzaga Del Moral, Maria Claudia Santos-Silva
BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a combination of morphology, immunophenotype, recurrent cytogenetic aberration and clinical features. However, even with these diagnostic tools, a definitive diagnosis can be difficult to achieve. Therefore, the aim of this study was to assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases. METHODS: To address this issue, we investigated the expression of CD39, CD43, CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to 2016...
May 16, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#13
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#14
Elizabeth Whittaker, Mark Nicol, Heather J Zar, Beate Kampmann
BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection. OBJECTIVE: To comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487312/complete-deletion-of-cd39-is-atheroprotective-in-apolipoprotein-e-deficient-mice
#15
Marco De Giorgi, Keiichi Enjyoji, Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Richard J Gumina, Ryszard T Smolenski, Simon C Robson
CD39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of CD39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE-/-) and Cd39/ApoE double knockout (Cd39-/-/ApoE-/-, DKO) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly less atherosclerotic lesions than ApoE KO mice, irrespective of diet...
May 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28472483/a-single-chain-antibody-cd39-fusion-protein-targeting-activated-platelets-protects-from-cardiac-ischaemia-reperfusion-injury
#16
Melanie Ziegler, Jan David Hohmann, Amy Kate Searle, Meike-Kristin Abraham, Harshal H Nandurkar, Xiaowei Wang, Karlheinz Peter
Aims: CD39 is a cell membrane NTPase with anti-inflammatory and anti-platelet effects. However, its clinical use is limited by its bleeding side effect. With the goal of harnessing its therapeutic potential while avoiding haemostatic problems, we designed a fusion protein consisting of the extracellular domain of CD39 and a single-chain antibody (Targ-CD39) that specifically binds to activated glycoprotein (GP)IIb/IIIa and thus to activated platelets. Through this enrichment at activated platelets, the required systemic dose is below the dose impairing haemostasis...
May 2, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28469075/bilirubin-suppresses-th17-immunity-in-colitis-by-upregulating-cd39
#17
Maria Serena Longhi, Marta Vuerich, Alireza Kalbasi, Jessica E Kenison, Ada Yeste, Eva Csizmadia, Byron Vaughn, Linda Feldbrugge, Shuji Mitshuhashi, Barbara Wegiel, Leo Otterbein, Alan Moss, Francisco J Quintana, Simon C Robson
Unconjugated bilirubin (UCB), a product of heme oxidation, has known immunosuppressant properties but the molecular mechanisms, other than antioxidant effects, remain largely unexplored. We note that UCB modulates T helper type 17 (Th17) immune responses, in a manner dependent upon heightened expression of CD39 ectonucleotidase. UCB has protective effects in experimental colitis, where it enhances recovery after injury and preferentially boosts IL-10 production by colonic intraepithelial CD4+ cells. In vitro, UCB confers immunoregulatory properties on human control Th17 cells, as reflected by increased levels of FOXP3 and CD39 with heightened cellular suppressor ability...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28462511/altered-expression-of-enos-prostacyclin-synthase-prostaglandin-g-h-synthase-and-thromboxane-synthase-in-porcine-aortic-endothelial-cells-after-exposure-to-human-serum-relevance-to-xenotransplantation
#18
Pengfei Chen, Hanchao Gao, Ying Lu, Huirong Nie, Zhaoming Liu, Yu Zhao, Nana Fan, Qingjian Zou, Yifan Dai, Aifa Tang, Hidetaka Hara, Zhiming Cai, David K C Cooper, Liangxue Lai, Lisha Mou
Under normal conditions, the activity of platelets is stringently and precisely balanced between activation and quiescent state. This guarantees rapid hemostasis and avoids uncontrolled thrombosis. However, excessive platelet activation and resulting thrombotic microangiopathy are frequently observed in pig-to-primate xenotransplantation models. Endothelium-derived inhibitory mechanisms play an important role in regulation of platelet activation. These mainly include nitric oxide (NO), prostacyclin PGI2 , and adenosine, which are synthesized by endothelial NO synthases (eNOS), prostacyclin synthase, and CD39/CD73, respectively...
April 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#19
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28414024/novel-high-throughput-cell-based-hybridoma-screening-methodology-using-the-celigo-image-cytometer
#20
Haohai Zhang, Leo Li-Ying Chan, William Rice, Nasim Kassam, Maria Serena Longhi, Haitao Zhao, Simon C Robson, Wenda Gao, Yan Wu
Hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. Technical issues associated with ELISA- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. Conventional ELISA screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain protein complexes...
April 14, 2017: Journal of Immunological Methods
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