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https://www.readbyqxmd.com/read/29683859/correlation-with-lymphocyte-infiltration-but-lack-of-prognostic-significance-of-meca-79-positive-high-endothelial-venules-in-primary-malignant-melanoma
#1
Tímea Sebestyén, Anita Mohos, Gabriella Liszkay, Beáta Somlai, István Gaudi, Andrea Ladányi
High endothelial venules (HEVs) are specialized vessels in lymphoid organs, supporting lymphocyte trafficking from the blood. As the presence of these vessels was described recently in tumors, it was proposed that they could facilitate the development of antitumor immune response, resulting in improved prognosis. The aim of our study was to analyze the correlation of the density of HEVs with that of the different immune cell types as well as with the clinicopathologic parameters and the disease outcomes in patients with cutaneous melanoma...
April 20, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#2
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29673902/la-ssb-chimeric-autoantibody-receptor-modified-nk92mi-cells-for-targeted-therapy-of-autoimmune-disease
#3
Huimin Meng, Xue Sun, Yanhui Song, Jianxuan Zou, Gangli An, Zeming Jin, Lin Yang
It has been long sought to specifically eliminate B-cell clones that generate autoreactive antibodies, while sparing the immune system when combating autoimmune disease. Although it was impossible to achieve this goal before, newly developed techniques have made it feasible today. Autoantibodies against La/SSB were involved in several autoimmune diseases. Here, we aimed to introduce La/SSB epitope-based chimeric autoantibody receptors (CAAR) into NK92MI cells enabled it to destroy the corresponding La/SSB-specific B cell receptor (BCR) -bearing lymphoma cells (LaA-BCR-Romas, LaA-BCR-Maver-1, and LaA-BCR-Jurkat cells)...
April 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29571029/cd137-a-checkpoint-regulator-involved-in-atherosclerosis
#4
REVIEW
Leif Å Söderström, Laura Tarnawski, Peder S Olofsson
Inflammation is associated with atherosclerotic plaque development and precipitation of myocardial infarction and stroke, and anti-inflammatory therapy may reduce disease severity. Costimulatory molecules are key regulators of immune cell activity and inflammation, and are associated with disease development in atherosclerosis. Accumulating evidence indicates that a costimulatory molecule of the Tumor Necrosis Factor Receptor superfamily, the checkpoint regulator CD137, promotes atherosclerosis and vascular inflammation in experimental models...
March 5, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29570193/phytol-stimulates-the-browning-of-white-adipocytes-through-the-activation-of-amp-activated-protein-kinase-ampk-%C3%AE-in-mice-fed-high-fat-diet
#5
Fenglin Zhang, Wei Ai, Xiaoquan Hu, Yingying Meng, Cong Yuan, Han Su, Lina Wang, Xiaotong Zhu, Ping Gao, Gang Shu, Qingyan Jiang, Songbo Wang
Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C)...
March 23, 2018: Food & Function
https://www.readbyqxmd.com/read/29568102/enhanced-hexose-6-phosphate-dehydrogenase-expression-in-adipose-tissue-may-contribute-to-diet-induced-visceral-adiposity
#6
Limei Liu, Ying Wang, Jian Wang, Yunzhou Dong, Scarlett Chang, Xiwen Liu, Kabirullah Lutfy, Hong Chen, Theodore C Friedman, Meisheng Jiang, Yanjun Liu
BACKGROUND: Visceral fat accumulation increases the risk of developing type 2 diabetes and metabolic syndrome, and is associated with excessive glucocorticoids (GCs). Fat depot-specific GC action is tightly controlled by 11ß-hydroxysteroid dehydrogenase (11ß-HSD1) coupled with the enzyme hexose-6-phosphate dehydrogenase (H6PDH). Mice with inactivation or activation of H6PDH genes show altered adipose 11ß-HSD1 activity and lipid storage. We hypothesized that adipose tissue H6PDH activation is a leading cause for the visceral obesity and insulin resistance...
February 22, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29549159/phase-i-study-of-single-agent-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-patients-with-advanced-cancer
#7
Neil H Segal, Aiwu R He, Toshihiko Doi, Ronald Levy, Shailender Bhatia, Michael J Pishvaian, Rossano Cesari, Ying Chen, Craig B Davis, Bo Huang, Aron D Thall, Ajay K Gopal
Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29547798/magnolol-promotes-thermogenesis-and-attenuates-oxidative-stress-in-3t3-l1-adipocytes
#8
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
https://www.readbyqxmd.com/read/29520276/alloreactive-t-cell-receptor-diversity-against-structurally-similar-or-dissimilar-hla-dp-antigens-assessed-by-deep-sequencing
#9
Esteban Arrieta-Bolaños, Pietro Crivello, Maximilian Metzing, Thuja Meurer, Müberra Ahci, Julie Rytlewski, Marissa Vignali, Erik Yusko, Peter van Balen, Peter A Horn, J H Frederik Falkenburg, Katharina Fleischhauer
T cell alloreactivity is mediated by a self-human leukocyte antigen (HLA)-restricted T cell receptor (TCR) repertoire able to recognize both structurally similar and dissimilar allogeneic HLA molecules (i.e., differing by a single or several amino acids in their peptide-binding groove). We hypothesized that thymic selection on self-HLA molecules could have an indirect impact on the size and diversity of the alloreactive response. To test this possibility, we used TCR Vβ immunophenotyping and immunosequencing technology in a model of alloreactivity between self-HLA selected T cells and allogeneic HLA-DPB1 (DPB1) differing from self-DPB1*04:02 by a single (DPB1*02:01) or several (DPB1*09:01) amino acids in the peptide-binding groove...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29503042/engrafting-human-regulatory-t-cells-with-a-flexible-modular-chimeric-antigen-receptor-technology
#10
Stefanie Koristka, Alexandra Kegler, Ralf Bergmann, Claudia Arndt, Anja Feldmann, Susann Albert, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Jan Moritz Middeke, Martin Bornhäuser, Marc Schmitz, Jens Pietzsch, Katja Akgün, Tjalf Ziemssen, Jörg Steinbach, Michael P Bachmann
As regulatory T cells (Tregs) play a fundamental role in immune homeostasis their adoptive transfer emerged as a promising treatment strategy for inflammation-related diseases. Preclinical animal models underline the superiority of antigen-specific Tregs compared to polyclonal cells. Here, we applied a modular chimeric antigen receptor (CAR) technology called UniCAR for generation of antigen-specific human Tregs. In contrast to conventional CARs, UniCAR-endowed Tregs are indirectly linked to their target cells via a separate targeting module (TM)...
March 1, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29489438/isolation-of-peripheral-blood-cd8-t-cells-specific-to-porcine-reproductive-and-respiratory-syndrome-virus-utilizing-porcine-cd137-activation-marker
#11
Sakthivel Subramaniam, Christopher Overend, Danielle M Yugo, C Lynn Heffron, Shannon R Matzinger, Adam J Rogers, Debin Tian, Qian M Cao, Scott P Kenney, Xiang-Jin Meng
CD137 is a costimulatory molecule transiently expressed on activated T cells after mitogen or antigen stimulation that can be exploited for isolating antigen-specific T cells as reported in mouse models. By utilizing an antiporcine CD137 monoclonal antibody (mAb, clone 3B9) developed in our laboratory, we isolated virus-specific CD8β T cells from peripheral blood of pigs experimentally infected with different porcine reproductive and respiratory syndrome virus (PRRSV) strains. Similar to mouse, porcine CD8β T cells also express CD137 transiently upon Concavalin A stimulation while the unstimulated cells did not...
February 28, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29487979/the-multi-receptor-inhibitor-axitinib-reverses-tumor-induced-immunosuppression-and-potentiates-treatment-with-immune-modulatory-antibodies-in-preclinical-murine-models
#12
Heinz Läubli, Philipp Müller, Lucia D'Amico, Mélanie Buchi, Abhishek S Kashyap, Alfred Zippelius
Cancer immunotherapies have significantly improved the prognosis of cancer patients. Despite the clinical success of targeting inhibitory checkpoint receptors, including PD-1 and/or CTLA-4 on T cells, only a minority of patients derive benefit from these therapies. New strategies to improve cancer immunotherapy are therefore needed. Combination therapy of checkpoint inhibitors with targeted agents has promisingly shown to increase the efficacy of immunotherapy. Here, we analyzed the immunomodulatory effects of the multi-receptor tyrosine kinase inhibitor axitinib and its efficacy in combination with immunotherapies...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29475880/identification-of-tumoricidal-tcrs-from-tumor-infiltrating-lymphocytes-by-single-cell-analysis
#13
Kiyomi Shitaoka, Hiroshi Hamana, Hiroyuki Kishi, Yoshihiro Hayakawa, Eiji Kobayashi, Kenta Sukegawa, Xiuhong Piao, Fulian Lyu, Takuya Nagata, Daisuke Sugiyama, Hiroyoshi Nishikawa, Atsushi Tanemura, Ichiro Katayama, Mutsunori Murahashi, Yasushi Takamatsu, Kenzaburo Tani, Tatsuhiko Ozawa, Atsushi Muraguchi
T-cell receptor (TCR) gene therapy is a promising next-generation antitumor treatment. We previously developed a single-T-cell analysis protocol that allows the rapid capture of paired TCRalpha and beta cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TILs) of various cancer patients. We found clonally expanded populations of T cells that expressed the same clonotypic TCR in 50 to 70% of CD137+CD8+ TILs, indicating that they responded to certain antigens in the tumor environment...
February 23, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29467769/cd137-cd154-expression-as-a-regulatory-t-cell-treg-specific-activation-signature-for-identification-and-sorting-of-stable-human-tregs-from-in-vitro-expansion-cultures
#14
Anna Nowak, Dominik Lock, Petra Bacher, Thordis Hohnstein, Katrin Vogt, Judith Gottfreund, Pascal Giehr, Julia K Polansky, Birgit Sawitzki, Andrew Kaiser, Jörn Walter, Alexander Scheffold
Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cultures is highly variable, and currently, it is impossible to identify and separate stable Tregs from contaminating effector T cells, either ex vivo or after prior expansion...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29454004/identification-and-analysis-of-peanut-specific-t-effector-and-t-regulatory-cells-in-children-allergic-and-tolerant-to-peanut
#15
Katherine A Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R Neeland, Mimi Lk Tang, Thanh D Dang, Katrina J Allen, Pamela A Frischmeyer-Guerrerio
BACKGROUND: Peanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear. OBJECTIVE: We sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization...
February 14, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29433059/resveratrol-liposomes-and-lipid-nanocarriers-comparison-of-characteristics-and-inducing-browning-of-white-adipocytes
#16
Yujiao Zu, Haley Overby, Guofeng Ren, Zhaoyang Fan, Ling Zhao, Shu Wang
Trans-resveratrol (R) has a potential to increase energy expenditure via inducing browning in white adipose tissue. However, its low levels of aqueous solubility, stability, and poor bioavailability limit its application. We have successfully synthesized biocompatible, and biodegradable R encapsulated lipid nanocarriers (R-nano), and R encapsulated liposomes (R-lipo). The mean particle size of R-nano and R-lipo were 140 nm and 110 nm, respectively, and their polydispersity index values were less than 0...
December 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29396470/augmentation-of-cd134-ox40-dependent-nk-anti-tumour-activity-is-dependent-on-antibody-cross-linking
#17
Anna H Turaj, Kerry L Cox, Christine A Penfold, Ruth R French, C Ian Mockridge, Jane E Willoughby, Alison L Tutt, Jordana Griffiths, Peter W M Johnson, Martin J Glennie, Ronald Levy, Mark S Cragg, Sean H Lim
CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies. Here, we examine the expression and function of CD134 on human and mouse NK cells in B-cell lymphoma. CD134 was transiently upregulated upon activation of NK cells in both species. In contrast to CD137, induction of CD134 on human NK cells was dependent on close proximity to, or cell-to-cell contact with, monocytes or T cells...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327109/a-novel-biologic-platform-elicits-profound-t-cell-costimulatory-activity-and-antitumor-immunity-in-mice
#18
Joseph M Ryan, Payal Mittal, Antoine Menoret, Julia Svedova, Jeffrey S Wasser, Adam J Adler, Anthony T Vella
Combination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, "OrthomAb", is shown...
April 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29325369/-cd137-signaling-promotes-the-formation-of-plaque-calcification-via-inhibiting-the-fusion-of-autophagy-and-lysosomal-in-apo-e-mice
#19
X Y Li, R Chen, W Zhong, B Li, C Shao, Z Q Wang, J C Yan
Objective: To investigate whether CD137 signaling promoted the formation of atherosclerotic plaque calcification by inhibiting the fusion of autophagosome and lysosome. Methods: (1) In vivo, CD137 agonist antibody and anti-CD137 antibody were used to stimulate and inhibit the CD137 signaling, respectively. Fifteen Apo E(-/-) mice were randomly divided into three groups: control group (intraperitoneal injection of IgG2b 200 µg) , CD137 agonist group (intraperitoneal injection of CD137 agonist antibody 200 µg) , anti-CD137 group (pretreatment with 200 µg anti-CD137 antibody for 24 hours, then injection of CD137 agonist antibody) ...
December 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29305435/an-immunotherapeutic-cd137-agonist-releases-eomesodermin-from-thpok-repression-in-cd4-t-cells
#20
Payal Mittal, Rebecca Abblett, Joseph M Ryan, Adam T Hagymasi, Archibald Agyekum-Yamoah, Julia Svedova, Steven L Reiner, Marie-Clare St Rose, Matthew P Hanley, Anthony T Vella, Adam J Adler
Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8+ and CD4+ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8+ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8+ CTLs...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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