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Myeloid regulatory cells

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https://www.readbyqxmd.com/read/28818704/orphan-drug-regulation-a-missed-opportunity-for-children-and-adolescents-with-cancer
#1
Gilles Vassal, Pam Kearns, Patricia Blanc, Nicole Scobie, Delphine Heenen, Andy Pearson
BACKGROUND: Oncology represents a major sector in the field of orphan drug development in Europe. The objective was to evaluate whether children and adolescents with cancer benefited from the Orphan Drug Regulation. METHODS: Data on orphan drug designations (ODDs) and registered orphan drugs from 8th August 2000 to 10th September 2016 were collected from the Community Register of medicinal products for human use. Assessment history, product information and existence of paediatric investigation plans were searched and retrieved from the European Medicine Agency website...
August 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#2
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#3
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808383/chemopreventive-potential-of-major-flavonoid-compound-of-methanolic-bark-extract-of-saraca-asoca-roxb-in-benzene-induced-toxicity-of-acute-myeloid-leukemia-mice
#4
Manas Kumar Mukhopadhyay, Mithun Shaw, Debjani Nath
BACKGROUND: Saraca asoca (SA) (Roxb.) is one of the folk medicinal plants found in India, Bangladesh, and Sri Lanka. Its major biological activity appears due to the presence of flavonoid group of compounds in its bark extract. OBJECTIVE: In this study, our research aims to analyze the chemopreventive effect of flavonoids, especially a natural phenol catechin present in the bark methanolic extract of SA on acute myeloid leukemia (AML) mice. MATERIALS AND METHODS: The total bark extract was partitioned and analyzed on thin-layer chromatography (TLC) plate...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807569/il-10-engineered-human-cd4-tr1-cells-eliminate-myeloid-leukemia-in-an-hla-class-i-dependent-mechanism
#5
Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models...
July 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28807056/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#6
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28805801/small-molecule-studies-identify-cdk8-as-a-regulator-of-il-10-in-myeloid-cells
#7
Liv Johannessen, Thomas B Sundberg, Daniel J O'Connell, Raivo Kolde, James Berstler, Katelyn J Billings, Bernard Khor, Brinton Seashore-Ludlow, Anne Fassl, Caitlin N Russell, Isabel J Latorre, Baishan Jiang, Daniel B Graham, Jose R Perez, Piotr Sicinski, Andrew J Phillips, Stuart L Schreiber, Nathanael S Gray, Alykhan F Shamji, Ramnik J Xavier
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation...
August 14, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28805251/wiskott-aldrich-syndrome-protein-emerging-mechanisms-in-immunity
#8
REVIEW
Elizabeth Rivers, Adrian J Thrasher
The Wiskott Aldrich syndrome protein (WASP) participates in innate and adaptive immunity through regulation of actin cytoskeleton-dependent cellular processes, including immune synapse formation, cell signaling, migration and cytokine release. There is also emerging evidence for a direct role in nuclear transcription programmes uncoupled from actin polymerization. A deeper understanding of some of the more complex features of Wiskott Aldrich syndrome (WAS) itself, such as the associated autoimmunity and inflammation, has come from identification of defects in the number and function of anti-inflammatory myeloid cells and regulatory T and B cells, as well as defects in positive and negative B-cell selection...
August 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28794406/the-non-coding-rna-landscape-of-human-hematopoiesis-and-leukemia
#9
Adrian Schwarzer, Stephan Emmrich, Franziska Schmidt, Dominik Beck, Michelle Ng, Christina Reimer, Felix Ferdinand Adams, Sarah Grasedieck, Damian Witte, Sebastian Käbler, Jason W H Wong, Anushi Shah, Yizhou Huang, Razan Jammal, Aliaksandra Maroz, Mojca Jongen-Lavrencic, Axel Schambach, Florian Kuchenbauer, John E Pimanda, Dirk Reinhardt, Dirk Heckl, Jan-Henning Klusmann
Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28790345/oleate-but-not-stearate-induces-the-regulatory-phenotype-of-myeloid-suppressor-cells
#10
Hao Wu, Carl Weidinger, Franziska Schmidt, Jacqueline Keye, Marie Friedrich, Cansu Yerinde, Gerald Willimsky, Zhihai Qin, Britta Siegmund, Rainer Glauben
Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#11
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28760770/transcriptional-mechanisms-that-control-expression-of-the-macrophage-colony-stimulating-factor-receptor-locus
#12
REVIEW
Rocio Rojo, Clare Pridans, David Langlais, David A Hume
The proliferation, differentiation, and survival of cells of the macrophage lineage depends upon signals from the macrophage colony-stimulating factor (CSF) receptor (CSF1R). CSF1R is expressed by embryonic macrophages and induced early in adult hematopoiesis, upon commitment of multipotent progenitors to the myeloid lineage. Transcriptional activation of CSF1R requires interaction between members of the E26 transformation-specific family of transcription factors (Ets) (notably PU.1), C/EBP, RUNX, AP-1/ATF, interferon regulatory factor (IRF), STAT, KLF, REL, FUS/TLS (fused in sarcoma/ranslocated in liposarcoma) families, and conserved regulatory elements within the mouse and human CSF1R locus...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28759306/skeletal-muscle-regeneration-involves-macrophage-myoblast-bonding
#13
Laura Cristina Ceafalan, Tudor Emanuel Fertig, Alexandru Cristian Popescu, Bogdan Ovidiu Popescu, Mihail Eugen Hinescu, Mihaela Gherghiceanu
Regeneration in adult skeletal muscle relies on the activation, proliferation, and fusion of myogenic precursor cells (MPC), mostly resident satellite cells (SC). However, the regulatory mechanism during this process is still under evaluation, with the final aim to manipulate regeneration when the intrinsic mechanism is corrupted. Furthermore, intercellular connections during skeletal muscle regeneration have not been previously thoroughly documented. Our hypothesis was that a direct and close cellular interaction between SC/MPC and invading myeloid cells is a key step in order to control regeneration...
July 31, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28757239/beyond-mrna-the-role-of-non-coding-rnas-in-normal-and-aberrant-hematopoiesis
#14
REVIEW
Mark C Wilkes, Claire E Repellin, Kathleen M Sakamoto
The role of non-coding Ribonucleic Acids (ncRNAs) in biology is currently an area of intense focus. Hematopoiesis requires rapidly changing regulatory molecules to guide appropriate differentiation and ncRNA are well suited for this. It is not surprising that virtually all aspects of hematopoiesis have roles for ncRNAs assigned to them and doubtlessly much more await characterization. Stem cell maintenance, lymphoid, myeloid and erythroid differentiation are all regulated by various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and various transposable elements within the genome...
July 25, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28754985/epigenetic-changes-in-myelofibrosis-distinct-methylation-changes-in-the-myeloid-compartments-and-in-cases-with-asxl1-mutations
#15
Helene Myrtue Nielsen, Christen Lykkegaard Andersen, Maj Westman, Lasse Sommer Kristensen, Fazila Asmar, Torben Arvid Kruse, Mads Thomassen, Thomas Stauffer Larsen, Vibe Skov, Lise Lotte Hansen, Ole Weis Bjerrum, Hans Carl Hasselbalch, Vasu Punj, Kirsten Grønbæk
This is the first study to compare genome-wide DNA methylation profiles of sorted blood cells from myelofibrosis (MF) patients and healthy controls. We found that differentially methylated CpG sites located to genes involved in 'cancer' and 'embryonic development' in MF CD34+ cells, in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation pattern using an unsupervised approach...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751524/micrornas-and-acute-myeloid-leukemia-therapeutic-implications-and-emerging-concepts
#16
Jared A Wallace, Ryan M O'Connell
Acute myeloid leukemia (AML) is a deadly hematologic malignancy characterized by the uncontrolled growth of immature myeloid cells. Over the past several decades we have learned a tremendous amount regarding the genetic aberrations that govern disease development in AML. Among these are genes that encode non-coding RNAs, including the microRNA (miRNA) family. miRNAs are evolutionary conserved small non-coding RNAs that display important physiological effects through their post-transcriptional regulation of messenger RNA (mRNA) targets...
July 27, 2017: Blood
https://www.readbyqxmd.com/read/28751190/septin-6-regulates-engraftment-and-lymphoid-differentiation-potential-of-murine-long-term-hematopoietic-stem-cells
#17
Katharina Senger, Gina Marka, Karin Soller, Vadim Sakk, Maria Carolina Florian, Hartmut Geiger
Septins are a family of filament-forming GTP-binding proteins that serve as scaffolds and diffusion barriers in various cellular processes. Septin 6 is known as a fusion partner of mixed-lineage leukemia (MLL) in infant acute myeloid leukemia (AML). The occurrence of the fusion gene is associated with a reduced expression of septin 6 itself. The role of septin 6 in hematopoiesis and whether it is involved in scaffolds within hematopoietic cells is not known. Septin 6 deficient hematopoietic stem cells (HSCs) presented with an increased engraftment potential but altered lymphoid differentiation with a reduced contribution to the T cell compartment and an increased B cell contribution...
July 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28750066/cross-modulation-of-pathogen-specific-pathways-enhances-malnutrition-during-enteric-co-infection-with-giardia-lamblia-and-enteroaggregative-escherichia-coli
#18
Luther A Bartelt, David T Bolick, Jordi Mayneris-Perxachs, Glynis L Kolling, Gregory L Medlock, Edna I Zaenker, Jeffery Donowitz, Rose Viguna Thomas-Beckett, Allison Rogala, Ian M Carroll, Steven M Singer, Jason Papin, Jonathan R Swann, Richard L Guerrant
Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens in malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we provide new insights into intersecting pathogen-specific mechanisms that enhance malnutrition. We show for the first time that during protein malnutrition, the intestinal microbiota permits persistent Giardia colonization and simultaneously contributes to growth impairment...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28747550/a-tyrosine-kinase-stat5-mir21-pdcd4-regulatory-axis-in-chronic-and-acute-myeloid-leukemia-cells
#19
Anne-Sophie Espadinha, Valérie Prouzet-Mauléon, Stéphane Claverol, Valérie Lagarde, Marc Bonneu, François-Xavier Mahon, Bruno Cardinaud
MicroRNAs (miRNAs) are regulators of several key patho-physiological processes, including cell cycle and apoptosis. Using microarray-based miRNA profiling in K562 cells, a model of chronic myeloid leukemia (CML), we found that the oncoprotein BCR-ABL1 regulates the expression of miR-21, an "onco-microRNA", found to be overexpressed in several cancers. This effect relies on the presence of two STAT binding sites on the promoter of miR-21, and on the phosphorylation status of STAT5, a transcription factor activated by the kinase activity of BCR-ABL1...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28736551/differential-phenotypes-of-myeloid-derived-suppressor-and-t-regulatory-cells-and-cytokine-levels-in-amnestic-mild-cognitive-impairment-subjects-compared-to-mild-alzheimer-diseased-patients
#20
Aurélie Le Page, Hugo Garneau, Gilles Dupuis, Eric H Frost, Anis Larbi, Jacek M Witkowski, Graham Pawelec, Tamàs Fülöp
Alzheimer disease (AD) is the most prevalent form of dementia although the underlying cause(s) remains unknown at this time. However, neuroinflammation is believed to play an important role and suspected contributing immune parameters can be revealed in studies comparing patients at the stage of amnestic mild cognitive impairment (aMCI) to healthy age-matched individuals. A network of immune regulatory cells including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) maintains immune homeostasis but there are very few data on the role of these cells in AD...
2017: Frontiers in Immunology
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