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OX40L

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https://www.readbyqxmd.com/read/29209565/tumor-targeted-costimulation-with-antibody-fusion-proteins-improves-bispecific-antibody-mediated-immune-response-in-presence-of-immunosuppressive-factors
#1
Sabrina Sapski, Nadine Beha, Roland Kontermann, Dafne Müller
Therapeutic strategies aiming for the induction of an effective immune response at the tumor site can be severely hampered by the encounter of an immunosuppressive microenvironment. We investigated here the potential of concerted costimulation by tumor-directed antibody-fusion proteins with B7.1, 4-1BBL and OX40L to enforce bispecific antibody-induced T cell stimulation in presence of recognized immunosuppressive factors including IL-10, TGF-β, indoleamine 2,3-dioxygenase (IDO), PD-L1 and regulatory T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29207606/combination-therapy-with-an-ox40l-fusion-protein-and-a-vaccine-targeting-the-transcription-factor-twist-inhibits-metastasis-in-a-murine-model-of-breast-cancer
#2
Anthony S Malamas, Scott A Hammond, Jeffrey Schlom, James W Hodge
OX40 is a costimulatory receptor that potentiates proliferation, survival, memory formation, and effector function of CD4+ and CD8+ T-cells, while overcoming the suppressive activity of regulatory T-cells (Tregs). Here, we explored the combination of an OX40L fusion protein (OX40L-FP) with a poxvirus-based cancer vaccine (MVA-Twist-TRICOM) to inhibit tumor metastasis in the 4T1 murine breast cancer model. Contrary to the single agent treatments, the combination therapy significantly decreased the number of metastatic colonies per lung and prolonged survival...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#3
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29147616/mrna-expression-levels-of-genes-involved-in-antitumor-immunity-identification-of-a-3-gene-signature-associated-with-prognosis-of-muscle-invasive-bladder-cancer
#4
Constance Le Goux, Sophie Vacher, Géraldine Pignot, Mathilde Sibony, Nicolas Barry Delongchamps, Benoit Terris, Eliane Piaggio, Marc Zerbib, Diane Damotte, Ivan Bieche
Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29124973/divergent-hypersensitivity-responses-following-topical-application-of-the-quaternary-ammonium-compound-didecyldimethylammonium-bromide
#5
Hillary L Shane, Ewa Lukomska, Aleksandr B Stefaniak, Stacey E Anderson
Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625-2%), evaluated by ear swelling in female BALB/c mice...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29118006/the-immunobiology-of-cd27-and-ox40-and-their-potential-as-targets-for-cancer-immunotherapy
#6
Sarah L Buchan, Anne Rogel, Aymen Al-Shamkhani
In recent years monoclonal antibodies (mAbs) able to reinvigorate anti-tumor T cell immunity have heralded a paradigm shift in cancer treatment. The most high profile of these mAbs block the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients across a range of tumor types. However, it is becoming increasingly clear that failure of some patients to respond to checkpoint inhibition is due to inadequate T-cell priming. For full T-cell activation two signals must be received and ligands providing the second of these signals, termed costimulation, are often lacking in tumors...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29100993/hepatitis-c-virus-induced-natural-killer-cell-proliferation-involves-monocyte-derived-cells-and-the-ox40-ox40l-axis
#7
Julia Pollmann, Jana-Julia Götz, Daniel Rupp, Otto Strauss, Markus Granzin, Oliver Grünvogel, Pascal Mutz, Catharina Kramer, Felix Lasitschka, Volker Lohmann, Niklas K Björkström, Robert Thimme, Ralf Bartenschlager, Adelheid Cerwenka
BACKGROUND AND AIMS: Natural killer (NK) cells are found at increased frequencies in hepatitis C virus (HCV)-infected patients. NK cell activation was shown to correlate with HCV clearance and to predict favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. METHODS: NK cell phenotype, proliferation, and function were assessed after six-day co-culture of human peripheral blood mononuclear cells (PBMCs) with HCV-replicon containing Huh6 hepatoblastoma cells or HCV-infected Huh7...
October 31, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29081529/transplantation-combining-ox40l-and-mtor-blockade
#8
Sarah Crunkhorn
No abstract text is available yet for this article.
October 30, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29024606/role-of-the-tslp-dc-ox40l-pathway-in-asthma-pathogenesis-and-airway-inflammation-in-mice
#9
Shuang Feng, Li Zhang, Xu-Hua Bian, Ying Luo, Guang-Hui Qin, Rui-Ming Shi
This study aims to explore the effect of the TSLP/DC/OX40L pathway in asthma pathogenesis and airway inflammation in mice. Sixty-five male BALF/c mice were divided into the control, asthma, IgG + asthma (IgG, 500 g/500 l, intratracheal injection of 50 l each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 ug/500 l TSLP antibody, 50 l each time) groups. ELISA was applied to measure the serum levels of IgE, ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13 and interferon-γ (IFN-γ), flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28974950/exploring-synergy-in-combinations-of-tumor-derived-vaccines-that-harbor-4-1bbl-ox40l-and-gm-csf
#10
Andrea J Manrique-Rincón, Camila M Beraldo, Jessica M Toscaro, Marcio C Bajgelman
Recent studies have demonstrated that combination of modulatory immune strategies may potentiate tumor cell elimination. Most strategies rely on the use of monoclonal antibodies that can block cell surface receptors to overcome tumor-induced immunosuppression or acting as costimulatory ligands to boost activation of T cells. In this study, we evaluate the use of combinations of genetically modified tumor-derived cell lines that harbor the costimulatory T cell ligands 4-1BB ligand, OX40L, and the cytokine GM-CSF...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#11
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#12
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28878335/systemic-lupus-erythematosus-ox40l-expressing-b-cells-promote-sle
#13
Jessica McHugh
No abstract text is available yet for this article.
October 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28818832/b-cell-ox40l-supports-t-follicular-helper-cell-development-and-contributes-to-sle-pathogenesis
#14
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunninghame Graham, Marina Botto, Timothy James Vyse
OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity...
August 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28747670/pkc-%C3%B1-is-dispensable-for-ox40l-induced-tcr-independent-treg-proliferation-but-contributes-by-enabling-il-2-production-from-effector-t-cells
#15
Khaled Alharshawi, Alejandra Marinelarena, Prabhakaran Kumar, Osama El-Sayed, Palash Bhattacharya, Zuoming Sun, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
We have previously shown that OX40L/OX40 interaction is critical for TCR-independent selective proliferation of Foxp3(+) Tregs, but not Foxp3(-) effector T-cells (Teff), when CD4(+) T-cells are co-cultured with GM-CSF derived bone marrow dendritic cells (G-BMDCs). Events downstream of OX40L/OX40 interaction in Tregs responsible for this novel mechanism are not understood. Earlier, OX40L/OX40 interaction has been shown to stimulate CD4(+) T-cells through the formation of a signalosome involving TRAF2/PKC-Ѳ leading to NF-kB activation...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696253/the-ox40-ox40-ligand-pathway-promotes-pathogenic-th-cell-responses-plasmablast-accumulation-and-lupus-nephritis-in-nzb-w-f1-mice
#16
Jonathan Sitrin, Eric Suto, Arthur Wuster, Jeffrey Eastham-Anderson, Jeong M Kim, Cary D Austin, Wyne P Lee, Timothy W Behrens
Ox40 ligand (Ox40L) locus genetic variants are associated with the risk for systemic lupus erythematosus (SLE); however, it is unclear how Ox40L contributes to SLE pathogenesis. In this study, we evaluated the contribution of Ox40L and its cognate receptor, Ox40, using in vivo agonist and antagonist approaches in the NZB × NZW (NZB/W) F1 mouse model of SLE. Ox40 was highly expressed on several CD4 Th cell subsets in the spleen and kidney of diseased mice, and expression correlated with disease severity. Treatment of aged NZB/W F1 mice with agonist anti-Ox40 mAbs potently exacerbated renal disease, which was accompanied by activation of kidney-infiltrating T cells and cytokine production...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#17
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28566332/oncolytic-adenovirus-and-tumor-targeting-immune-modulatory-therapy-improve-autologous-cancer-vaccination
#18
Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M Vence, Ying Yuan, Frederick F Lang, Carlo Toniatti, Mohammad B Hossain, Juan Fueyo
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L)...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28493549/transcription-factor-rbp-j-mediated-signalling-regulates-basophil-immunoregulatory-function-in-mouse-asthma-model
#19
Shuo-Yao Qu, Ya-Long He, Jian Zhang, Chang-Gui Wu
Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma...
September 2017: Immunology
https://www.readbyqxmd.com/read/28420813/establishment-of-cell-lines-from-adult-t-cell-leukemia-cells-dependent-on-negatively-charged-polymers
#20
Yoshitoyo Kagami, Susumu Uchiyama, Harumi Kato, Yasutaka Okada, Masao Seto, Tomohiro Kinoshita
Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here, we examined the effects of static electricity in the culture medium on the proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in vitro and thus had to be cultured in a medium containing negatively charged polymers. In the presence of poly-γ-glutamic acid (PGA) or chondroitin sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing OX40L (OX40L(+)HK)...
July 5, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
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