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immune tolerance OR anergy OR deletion

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https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#1
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28449211/operational-tolerance-in-kidney-transplantation-and-associated-biomarkers
#2
REVIEW
Annick Massart, Lidia Ghisdal, Marc Abramowicz, Daniel Abramowicz
In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel to this success, or perhaps because of it, we lost the battle for long-lived transplants, being overwhelmed with chronic immune insults and the toxicities of immunosuppression. It is likely that current powerful treatments block acute rejection, but at the same time condemn the few circulating donor cells that would have been able to elicit immunoregulatory host responses towards the allograft...
April 27, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28448022/development-of-an-economical-dna-delivery-system-by-acufection-and-its-application-to-skin-research
#3
Yu-Jei Lin, Tsung-Lin Lee, Chia-Chi Ku
Dysregulation of immune response in skin is associated with numerous human skin disorders. Direct transfer of immune-related genes into skin tissue is a fascinating approach to investigate immune modulation of cutaneous inflammation in mouse models of human diseases. Here we present a cost-effective protocol that delivered naked DNA in mouse skin and leads to transgene expression. The method is coined "acufection", denoting acupuncture-mediated DNA transfection. To perform acufection, mouse skin was first infused with DNA in phosphate-buffered saline (PBS) and then pricked lightly with a bundle of acupuncture needles to facilitate the absorption of DNA and transfection into cells...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28448002/measurement-of-t-cell-alloreactivity-using-imaging-flow-cytometry
#4
Stephen C Juvet, Sajad Moshkelgosha, Sharon Sanderson, Joanna Hester, Kathryn J Wood, Andrew Bushell
The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447409/factor-viii-inhibitors-advances-in-basic-and-translational-science
#5
REVIEW
J D Lai, D Lillicrap
In the treatment of hemophilia A, the 20%-30% risk of developing of anti-factor VIII (FVIII) antibodies, or inhibitors, is the dominant concern among healthcare providers. Immune tolerance induction remains the only effective method of eradicating inhibitors in approximately 75% of patients, but is accompanied by significant emotional and economical burden. While certain risk factors, such as the type of FVIII mutation, offer some insight, there remains no strategy to confidently predict the development of an inhibitor...
May 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28447368/optimization-of-aqueous-extraction-and-biological-activity-of-harpagophytum-procumbens-root-on-ex-vivo-rat-colon-inflammatory-model
#6
Marcello Locatelli, Claudio Ferrante, Simone Carradori, Daniela Secci, Lidia Leporini, Annalisa Chiavaroli, Sheila Leone, Lucia Recinella, Giustino Orlando, Sara Martinotti, Luigi Brunetti, Michele Vacca, Luigi Menghini
Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1-1000 μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28446465/deletion-of-lactate-dehydrogenase-a-in-myeloid-cells-triggers-antitumor-immunity
#7
Pankaj Seth, Eva Csizmadia, Andreas Hedblom, Marta Vuerich, Han Xie, Mailin Li, Maria Serena Longhi, Barbara Wegiel
Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis; diminished numbers of PD-L1+ cancer cells; increased numbers of CD3+ T cells and activation status of CD8+ T cells...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28445957/peripheral-kynurenine-tryptophan-ratio-is-not-a-reliable-marker-of-systemic-indoleamine-2-3-dioxygenase-a-lesson-drawn-from-patients-on-hemodialysis
#8
Yuanhan Chen, Zhen Xie, Chenggen Xiao, Min Zhang, Zhilian Li, Jianteng Xie, Yusheng Zhang, Xingchen Zhao, Pengfei Zeng, Liyi Mo, Xinling Liang, Wei Shi
Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445927/vaccines-targeting-pres1-domain-overcome-immune-tolerance-in-hbv-carrier-mice
#9
Yingjie Bian, Zheng Zhang, Zhichen Sun, Juanjuan Zhao, Danming Zhu, Yang Wang, Sherry Fu, Jingya Guo, Longchao Liu, Lishan Su, Fu-Sheng Wang, Yang-Xin Fu, Hua Peng
Strong tolerance to HBV surface antigens limits the therapeutic effect of the conventional HBsAg vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of preS1 region could improve therapy gain, we explored vaccination with the long peptide of preS1 domain for HBV virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg vaccination induced robust immune responses in the HBV carrier mice...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28445724/quantification-of-the-impact-of-the-hiv-1-glycan-shield-on-antibody-elicitation
#10
Tongqing Zhou, Nicole A Doria-Rose, Cheng Cheng, Guillaume B E Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D Schmidt, Kai Xu, Lei Chen, Rita E Chen, Mark K Louder, Marie Pancera, Timothy G Wanninger, Baoshan Zhang, Anqi Zheng, S Katie Farney, Kathryn E Foulds, Ivelin S Georgiev, M Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G Scorpio, Lawrence Shapiro, Adrian B McDermott, John R Mascola, Peter D Kwong
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character)...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#11
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways...
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445245/ectopic-expression-of-innate-immune-protein-lipocalin-2-in-lactococcus-lactis-protects-against-gut-and-environmental-stressors
#12
Piu Saha, Benoit Chassaing, Beng San Yeoh, Emilie Viennois, Xia Xiao, Mary J Kennett, Vishal Singh, Matam Vijay-Kumar
BACKGROUND: Lipocalin-2 (Lcn2) is a multifunctional innate immune protein that exhibits antimicrobial activity by the sequestration of bacterial siderophores, regulates iron homeostasis, and augments cellular tolerance to oxidative stress. Studies in the murine model of colitis have demonstrated that Lcn2 deficiency exacerbates colitogenesis; however, the therapeutic potential of Lcn2 supplementation has yet to be elucidated. In light of its potential mucoprotective functions, we, herein, investigated whether expression of Lcn2 in the probiotic bacterium can be exploited to alleviate experimental colitis...
April 25, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28444658/comparing-the-immune-genomic-effects-of-vilazodone-and-paroxetine-in-late-life-depression-a-pilot-study
#13
Harris Eyre, Prabha Siddarth, Natalie Cyr, Hongyu Yang, Steve Cole, Malcolm Forbes, Helen Lavretsky
Vilazodone is a novel antidepressant agent that combines selective serotonin (5-HT) reuptake inhibitor (SSRI) activity and 5-HT(1A) receptor partial agonist activity. A pilot study was conducted to compare vilazodone (novel compound) and paroxetine (gold standard) on antidepressant effects, tolerability, and inflammation and immune modulation. A 12-week, double-blind, randomized clinical trial was conducted with 56 nondemented older adults diagnosed with major depressive disorder (MDD). Between-group differences in mood, tolerability, and safety, as well as genomic markers of inflammation and immune modulation, were examined...
April 25, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28444424/the-experience-of-immune-checkpoint-inhibitors-in-chinese-patients-with-metastatic-melanoma-a-retrospective-case-series
#14
Xizhi Wen, Ya Ding, Jingjing Li, Jingjing Zhao, Ruiqing Peng, Dandan Li, Baoyan Zhu, Yao Wang, Xing Zhang, Xiaoshi Zhang
Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively...
April 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28444181/allogeneic-human-mesenchymal-stem-cell-infusions-for-aging-frailty
#15
Samuel Golpanian, Darcy L DiFede, Aisha Khan, Ivonne Hernandez Schulman, Ana Marie Landin, Bryon A Tompkins, Alan W Heldman, Roberto Miki, Bradley J Goldstein, Muzammil Mushtaq, Silvina Levis-Dusseau, John J Byrnes, Maureen Lowery, Makoto Natsumeda, Cindy Delgado, Russell Saltzman, Mayra Vidro-Casiano, Marietsy V Pujol, Moisaniel Da Fonseca, Anthony A Oliva, Geoff Green, Courtney Premer, Audrey Medina, Krystalenia Valasaki, Victoria Florea, Erica Anderson, Jill El-Khorazaty, Adam Mendizabal, Pascal J Goldschmidt-Clermont, Joshua M Hare
Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty. Methods: In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5)...
April 21, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28443380/acute-hypersensitivity-reaction-to-crotalidae-polyvalent-immune-fab-crofab-as-initial-presentation-of-galactose-%C3%AE-1-3-galactose-%C3%AE-gal-allergy
#16
Justin Rizer, Kaitlin Brill, Nathan Charlton, Joshua King
Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV...
April 26, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28443090/immunometabolic-regulations-mediated-by-coinhibitory-receptors-and-their-impact-on-t-cell-immune-responses
#17
REVIEW
Nikolaos Patsoukis, Jessica D Weaver, Laura Strauss, Christoph Herbel, Pankaj Seth, Vassiliki A Boussiotis
Host immunity provides wide spectrum protection that serves to eradicate pathogens and cancer cells, while maintaining self-tolerance and immunological homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling pathways that coordinately induce aerobic glycolysis, mitochondrial activity, anabolic metabolism, and T effector cell differentiation. Activation of PI3K, Akt, and mTOR triggers the switch to anabolic metabolism by inducing transcription factors such as Myc and HIF1, and the glucose transporter Glut1, which is pivotal for the increase of glucose uptake after T cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28443071/deletion-of-lipoteichoic-acid-synthase-impacts-expression-of-genes-encoding-cell-surface-proteins-in-lactobacillus-acidophilus
#18
Kurt Selle, Yong J Goh, Brant R Johnson, Sarah O'Flaherty, Joakim M Andersen, Rodolphe Barrangou, Todd R Klaenhammer
Lactobacillus acidophilus NCFM is a well-characterized probiotic microorganism, supported by a decade of genomic and functional phenotypic investigations. L. acidophilus deficient in lipoteichoic acid (LTA), a major immunostimulant in Gram-positive bacteria, has been shown to shift immune system responses in animal disease models. However, the pleiotropic effects of removing LTA from the cell surface in lactobacilli are unknown. In this study, we surveyed the global transcriptional and extracellular protein profiles of two strains of L...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#19
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4(+) T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8(+) T cell activation...
April 25, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28442414/inhibition-of-allogeneic-cytotoxic-t-cell-cd8-proliferation-via-polymer-induced-treg-cd4-cells
#20
Ning Kang, Wendy M Toyofuku, Xining Yang, Mark D Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8(+)) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8(+) and CD4(+) alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model...
April 22, 2017: Acta Biomaterialia
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