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Immunosuppression

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https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#1
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723551/understanding-immunosuppression-after-sepsis
#2
Fatemeh Fattahi, Peter A Ward
Following a severe primary infection or trauma, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. In this issue of Immunity, Roquilly et al. (2017) show that dendritic cells and macrophages developing in the lung after the resolution of a severe infection acquire tolerogenic properties that contribute to persistent immunosuppression and susceptibility to secondary infections.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#3
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723333/enhanced-prophylaxis-plus-antiretroviral-therapy-for-advanced-hiv-infection-in-africa
#4
James Hakim, Victor Musiime, Alex J Szubert, Jane Mallewa, Abraham Siika, Clara Agutu, Simon Walker, Sarah L Pett, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Symon Kaunda, Mercy Karoney, Godfrey Musoro, Sheila Kabahenda, Kusum Nathoo, Kathryn Maitland, Anna Griffiths, Margaret J Thomason, Cissy Kityo, Peter Mugyenyi, Andrew J Prendergast, A Sarah Walker, Diana M Gibb
Background In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. Methods In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter...
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28722500/post-marketing-surveillance-study-of-the-long-term-use-of-mizoribine-for-the-treatment-of-lupus-nephritis-2-year-results
#5
Tsutomu Takeuchi, Kenya Okada, Hisao Yoshida, Nobuyuki Yagi
OBJECTIVES: To understand the status of mizoribine use in patients with lupus nephritis (LN) and to collect safety- and efficacy-related data on 2-year treatment with mizoribine. METHODS: A continuous survey was conducted between March 2010 and July 2015. RESULTS: The analysis set included 559 patients (mean age 39.5 years, females 82.6%, mean duration of systemic lupus erythematosus (SLE) 8.4 years, mean duration of LN 5.9 years). Renal function was satisfactory for 6 months, but worsened from 12 months, with significant worsening at 24 months...
July 19, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#6
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#7
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Volker Eckstein, Anthony Ho, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31(-)-memory Tregs/Tresps led to differences in the suppressive activity of naïve and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721859/immunogenicity-and-safety-of-the-inactivated-hepatitis-a-vaccine-in-children-with-juvenile-idiopathic-arthritis-on-methotrexate-treatment-a-matched-case-control-study
#8
Despoina N Maritsi, Susan E Coffin, Ioanna Argyri, George Vartzelis, Nick Spyridis, Maria N Tsolia
OBJECTIVES: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. METHODS: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months...
July 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28721465/growth-of-children-born-to-renal-transplanted-women
#9
M Isabel S Dinelli, Erika Ono, Patrícia O Viana, Amélia M N Dos Santos, M Isabel de Moraes-Pinto
Neonates born to transplanted mothers are exposed to immunosuppressive drugs during gestation and have a higher risk of being born prematurely and small for gestational age than the general population. We have prospectively followed up 27 children born to renal transplanted mothers from a single center and 31 healthy children born at term with adequate weight for gestational age. Comparisons of weight and length measurements were made at birth, 1 month (±0.9), 3 months (±1.0), 6 months (±1.0), 9 months (±1...
July 18, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#10
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#11
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
https://www.readbyqxmd.com/read/28720716/pi3k%C3%AE-activity-in-leukocytes-promotes-adipose-tissue-inflammation-and-early-onset-insulin-resistance-during-obesity
#12
Ludovic Breasson, Barbara Becattini, Claudia Sardi, Angela Molinaro, Fabio Zani, Romina Marone, Fabrizio Botindari, Mélanie Bousquenaud, Curzio Ruegg, Matthias P Wymann, Giovanni Solinas
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet-induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720540/formulations-and-toxicologic-in-vivo-studies-of-aqueous-cyclosporin-a-eye-drops-with-cyclodextrin-nanoparticles
#13
Sunna Jóhannsdóttir, Johannes K Kristinsson, Zoltán Fülöp, GuÐrún Ásgrímsdóttir, Einar Stefánsson, Thorsteinn Loftsson
Cyclosporin A (CyA) is an immunosuppressive drug used topically to treat ocular inflammatory disorder such as dry eye disease (DES). It is a lipophilic cyclic peptide with molecular weight of 1202.6Da. The aim of this study was to develop surfactant free aqueous 0.2% (w/v) CyA eye drops where the drug is present in an aqueous vehicle containing CyA/cyclodextrin (CyA/CD) nanoparticles and then do three-month toxicological testing in rabbits. Five formulations of different CD concentrations were studied, all of them contained 12...
July 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#14
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720396/pituitary-adenylate-cyclase-activating-polypeptide-pacap-protects-against-mitoxantrone-induced-cardiac-injury-in-mice
#15
Venkat Subramaniam, Gin Chuang, Huijing Xia, Brendan Burn, Jessica Bradley, Jerome L Maderdrut, David H Coy, Kurt J Varner
Mitoxantrone (MXT) is an androstenedione that is used to treat cancers and progressive forms of multiple sclerosis; however, its use is limited by its cardiotoxicity. Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin/growth hormone-releasing hormone/vasoactive intestinal peptide family and has many functions, including cytoprotection and immunosuppression. We tested the hypothesis that PACAP can protect against MXT-induced cardiotoxicity in mice. Female BALB/c mice were treated once weekly for 4 weeks with saline (n=14) or MXT (3mg/kg, i...
July 15, 2017: Peptides
https://www.readbyqxmd.com/read/28720125/profiling-of-the-perturbed-metabolomic-state-of-mouse-spleen-during-acute-and-chronic-toxoplasmosis
#16
Xiao-Qing Chen, Chun-Xue Zhou, Hany M Elsheikha, Shuai He, Gui-Xue Hu, Xing-Quan Zhu
BACKGROUND: Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host's immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T...
July 18, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28719723/de-novo-hhv-8-tumors-induced-by-rituximab-in-autoimmune-or-inflammatory-systemic-diseases
#17
Amandine Perier, Léa Savey, Anne-Geneviève Marcelin, Philippe Serve, David Saadoun, Stéphane Barete
OBJECTIVES: HHV-8, also known as Kaposi's sarcoma (KS) associated herpesvirus is involved in KS and other tumors comprising multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). Rituximab is currently used for treatment of several autoimmune or inflammatory diseases and humoral organ rejection. De novo HHV-8 induced tumors by rituximab used for autoimmune or inflammatory diseases or humoral organ rejection have not been reported. METHODS: In this retrospective study, we report clinical, virological and pathology of five HIV-negative male patients with HHV-8-induced tumors following rituximab therapy...
July 18, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28719632/viscum-album-neutralizes-tumor-induced-immunosuppression-in-a-human-in-vitro-cell-model
#18
Carmen Steinborn, Amy Marisa Klemd, Ann-Sophie Sanchez-Campillo, Sophie Rieger, Marieke Scheffen, Barbara Sauer, Manuel Garcia-Käufer, Konrad Urech, Marie Follo, Annekathrin Ücker, Gunver Sophia Kienle, Roman Huber, Carsten Gründemann
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays...
2017: PloS One
https://www.readbyqxmd.com/read/28719615/a-human-tissue-based-functional-assay-platform-to-evaluate-the-immune-function-impact-of-small-molecule-inhibitors-that-target-the-immune-system
#19
Cristina St Pierre, Jane Guo, John D Shin, Laura W Engstrom, Hyun-Hee Lee, Alan Herbert, Laura Surdi, James Baker, Michael Salmon, Sanjiv Shah, J Michael Ellis, Hani Houshyar, Michael A Crackower, Melanie A Kleinschek, Dallas C Jones, Alexandra Hicks, Dennis M Zaller, Stephen E Alves, Ravisankar A Ramadas
While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#20
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
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