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CD40 Ligand

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https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#1
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28422751/twelve-year-survival-and-immune-correlates-in-dendritic-cell-vaccinated-melanoma-patients
#2
Stefanie Gross, Michael Erdmann, Ina Haendle, Steve Voland, Thomas Berger, Erwin Schultz, Erwin Strasser, Peter Dankerl, Rolf Janka, Stefan Schliep, Lucie Heinzerling, Karl Sotlar, Pierre Coulie, Gerold Schuler, Beatrice Schuler-Thurner
BACKGROUND: Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup. METHODS: Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28421990/elevated-levels-of-soluble-cd40-ligand-are-associated-with-antiphospholipid-antibodies-in-patients-with-systemic-lupus-erythematosus
#3
Ki-Jo Kim, In-Woon Baek, Chong-Hyeon Yoon, Wan-Uk Kim, Chul-Soo Cho
OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28416578/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#4
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28379034/lipoprotein-apheresis-in-the-treatment-of-dyslipidaemia-the-czech-republic-experience
#5
V Bláha, M Bláha, M Lánská, D Solichová, L Kujovská Krčmová, E Havel, P Vyroubal, Z Zadák, P Žák, L Sobotka
In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hypercholesterolemic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6+/-13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterolemia (FH): 5 homozygous, 9 heterozygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using hemorheopheresis...
April 5, 2017: Physiological Research
https://www.readbyqxmd.com/read/28369442/cd40-cd40l-crosstalk-drives-fascin-expression-in-dendritic-cells-for-efficient-antigen-presentation-to-cd4-t-cells
#6
Diana Elizondo, Temesgen Andargie, Dineeta Kubhar, Ayele Gugssa, Michael Lipscomb
Fascin is an actin bundling protein that, among immune cells, is restricted to expression in dendritic cells (DC). Previous reports have suggested that fascin plays an important role in governing DC antigen presentation to CD4+ T cells. However, no report has clearly linked the receptor-ligand engagement that can direct downstream regulation of fascin expression. In this study, bone marrow-derived DC from wild type vs. CD40-knockout C57BL/6 mice were used to elucidate the mechanisms of fascin expression and activity upon CD40-CD40 ligand (CD40L) engagement...
March 23, 2017: International Immunology
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#7
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28342978/a-new-benzenediamine-derivative-modulates-toll-like-receptors-induced-myeloid-dendritic-cells-activation-and-ameliorates-lupus-like-syndrome-in-mrllpr-lpr-mice
#8
Sheng Gao, Yongsheng Gong, Jianjian Ji, Linbo Yuan, Liping Han, Yimin Guo, Xiaofang Fan, Yayi Hou, Chunyan Hua
Modulators of the over-activation of myeloid dendritic cells (mDCs) by Toll-like receptors (TLRs) have an advantage in the treatment of systemic lupus erythematosus (SLE). This study was designed to evaluate the effects of FC-99, a novel benzenediamine derivative, on TLR-induced activation of mDCs, and to assess the efficacy of FC-99 in a murine model of SLE. In vitro, FC-99 inhibited the phenotypic (CD40 and MHC-II) and functional activation (IL-12 and CXCL10) of mDCs induced by TLR ligands. In vivo, MRLlpr/lpr mice displayed renal diseases associated with increased levels of proteinuria and immunoglobulin, which were ameliorated by FC-99...
May 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28339909/il-17-and-cd40-ligand-synergistically-stimulate-the-chronicity-of-diabetic-nephropathy
#9
Huey-Liang Kuo, Chiu-Ching Huang, Tze-Yi Lin, Ching-Yuang Lin
Background.: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods.: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 +  IL-17 +  T cells...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28314864/systematic-model-of-peripheral-inflammation-after-subarachnoid-hemorrhage
#10
Jude P J Savarraj, Kaushik Parsha, Georgene W Hergenroeder, Liang Zhu, Suhas S Bajgur, Sungho Ahn, Kiwon Lee, Tiffany Chang, Dong H Kim, Yin Liu, H Alex Choi
OBJECTIVE: To investigate inflammatory processes after aneurysmal subarachnoid hemorrhage (aSAH) with network models. METHODS: This is a retrospective observational study of serum samples from 45 participants with aSAH analyzed at multiple predetermined time points: <24 hours, 24 to 48 hours, 3 to 5 days, and 6 to 8 days after aSAH. Concentrations of cytokines were measured with a 41-plex human immunoassay kit, and the Pearson correlation coefficients between all possible cytokine pairs were computed...
March 17, 2017: Neurology
https://www.readbyqxmd.com/read/28298564/proteomic-analysis-of-sera-from-individuals-with-diffuse-cutaneous-systemic-sclerosis-reveals-a-multianalyte-signature-associated-with-clinical-improvement-during-imatinib-mesylate-treatment
#11
D James Haddon, Hannah E Wand, Justin A Jarrell, Robert F Spiera, Paul J Utz, Jessica K Gordon, Lorinda S Chung
OBJECTIVE: Imatinib has been investigated for the treatment of systemic sclerosis (SSc) because of its ability to inhibit the platelet-derived growth factor receptor and transforming growth factor-β signaling pathways, which have been implicated in SSc pathogenesis. In a 12-month open-label clinical trial assessing the safety and efficacy of imatinib in the treatment of diffuse cutaneous SSc (dcSSc), significant improvements in skin thickening were observed. Here, we report our analysis of sera collected during the clinical trial...
March 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28287031/comparison-of-diverse-platelet-activation-markers-as-indicators-for-left-atrial-thrombus-in-atrial-fibrillation
#12
Daniel Tarnowski, David M Poitz, Lina Plichta, Felix M Heidrich, Stephan Wiedemann, Tobias Ruf, Johannes Mierke, Tobias Löhn, Stefanie Jellinghaus, Ruth H Strasser, Karim Ibrahim, Christian Pfluecke
Atrial fibrillation (AF) is well known for being a major risk factor of thromboembolic stroke. We could recently demonstrate an association of monocyte-platelet aggregates (MPAs) with the degree of thrombogenicity in patients with AF. This study investigated platelet activation markers, as potential biomarkers for the presence of left atrial (LA) thrombus in patients with AF. One hundred and eight patients with symptomatic AF underwent transesophageal echocardiography (TEE) before scheduled cardioversion or pulmonary vein isolation...
March 13, 2017: Platelets
https://www.readbyqxmd.com/read/28284329/soluble-cd40-ligand-contributes-to-blood-brain-barrier-breakdown-and-central-nervous-system-inflammation-in-multiple-sclerosis-and-neuromyelitis-optica-spectrum-disorder
#13
Hiroki Masuda, Masahiro Mori, Tomohiko Uchida, Akiyuki Uzawa, Ryohei Ohtani, Satoshi Kuwabara
Soluble CD40 ligand (sCD40L) is reported to disrupt the blood-brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD40L levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD40L levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD40L levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28275176/human-bronchial-epithelium-orchestrates-dendritic-cell-activation-in-severe-asthma
#14
Delphine Gras, Asuncion Martinez-Anton, Arnaud Bourdin, Celine Garulli, Laure de Senneville, Isabelle Vachier, Joana Vitte, Pascal Chanez
The innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL)8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma.For this purpose, we investigated epithelial-dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk. Air-liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC)...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28267402/cd40-ligand-is-increased-in-mast-cells-in-psoriasis-and-actinic-keratosis-but-less-so-in-epithelial-skin-carcinomas
#15
Salla Haimakainen, Antti P Kaukinen, Mireille-Maria Suttle, Jukka Pelkonen, Ilkka T Harvima
The expression of CD40 ligand (CD40L) in mast cells was investigated in biopsies from lesional and non-lesional skin samples of patients with psoriasis, actinic keratosis (AK), basal cell carcinoma, and squamous cell carcinoma using a sequential double-staining technique. The percentage of CD40L(+) mast cells was higher in the lesional than in the non-lesional skin (p < .003). Interestingly, this percentage was lower in both carcinomas than in psoriasis and actinic keratosis (p < .025). Cells immunopositive for CD40 receptor were increased in all lesion types but especially so in carcinomas...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28261209/gm-csf-inhibits-c-kit-and-scf-expression-by-bone-marrow-derived-dendritic-cells
#16
Amairelys Belen Barroeta Seijas, Sonia Simonetti, Sara Vitale, Daniele Runci, Angela Caterina Quinci, Alessandra Soriani, Mattia Criscuoli, Irene Filippi, Antonella Naldini, Federico Maria Sacchetti, Umberto Tarantino, Francesco Oliva, Eleonora Piccirilli, Angela Santoni, Francesca Di Rosa
Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28239379/estrogen-receptor-dependent-regulation-of-dendritic-cell-development-and-function
#17
REVIEW
Sophie Laffont, Cyril Seillet, Jean-Charles Guéry
Autoimmunity, infectious diseases and cancer affect women and men differently. Because they tend to develop more vigorous adaptive immune responses than men, women are less susceptible to some infectious diseases but also at higher risk of autoimmunity. The regulation of immune responses by sex-dependent factors probably involves several non-redundant mechanisms. A privileged area of study, however, concerns the role of sex steroid hormones in the biology of innate immune cells, especially dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28235773/tlr10-suppresses-the-activation-and-differentiation-of-monocytes-with-effects-on-dc-mediated-adaptive-immune-responses
#18
Nicholas J Hess, Christopher Felicelli, Jennifer Grage, Richard I Tapping
TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation...
February 24, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28214521/neuroprotective-effect-of-salvianolic-acid-b-against-cerebral-ischemic-injury-in-rats-via-the-cd40-nf-%C3%AE%C2%BAb-pathway-associated-with-suppression-of-platelets-activation-and-neuroinflammation
#19
Shixin Xu, Aiqin Zhong, Huining Ma, Dan Li, Yue Hu, Yingzhi Xu, Junping Zhang
Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases...
April 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28208125/mean-platelet-volume-in-heterozygous-beta-thalassaemia
#20
Mehmet Ali Cikrikcioglu, Kenan Celik, Iskender Ekinci, Muharrem Nasifov, Aybala Erek Toprak, Guven Cetin, Sema Genc
BACKGROUND/AIM: It is not known why cerebrovascular and cardiovascular ischaemic events are less frequently observed in heterozygous beta thalassaemia (HBT) patients than in the general population. However, we previously reported that serum levels of some platelet function markers, i.e. soluble CD40 ligand and soluble P-selectin, are lower in patients with HBT than in controls. A high mean platelet volume (MPV) is an indicator of in vivo platelet activation and may indicate a tendency to thrombosis...
2017: Acta Haematologica
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