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Regulatory T lymphocyte

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https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#1
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#2
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28426141/melanocortin-2-3-and-4-receptor-gene-expressions-are-downregulated-in-cd8-t-cytotoxic-lymphocytes-and-cd19-b-lymphocytes-in-rheumatoid-arthritis-responding-to-tnf%C3%AE-inhibition
#3
Marlene Andersen, Ivan Nagaev, Michael Kruse Meyer, Olga Nagaeva, Jarl Wikberg, Lucia Mincheva-Nilsson, Grethe Neumann Andersen
Melanocortin signaling in leukocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signaling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptor (MC1-5R) gene expressions in pathogenetic leukocyte subsets in rheumatoid arthritis (RA) to treatment with TNFα inhibitor adalimumab. Seven patients with active RA donated blood at start and at three months treatment...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#4
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423487/ipilimumab-treatment-decreases-monocytic-mdscs-and-increases-cd8-effector-memory-t-cells-in-long-term-survivors-with-advanced-melanoma
#5
Yago Pico de Coaña, Maria Wolodarski, Isabel Poschke, Yuya Yoshimoto, Yuan Yang, Maria Nyström, Ulrika Edbäck, Suzanne Eghyazi Brage, Andreas Lundqvist, Giuseppe V Masucci, Johan Hansson, Rolf Kiessling
Ipilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. In this work, the immune system of ipilimumab treated patients was monitored to investigate potential mechanisms of action that may correlate with treatment outcome. Blood samples from 43 advanced melanoma patients were taken before, during and at the end of treatment. Hematological parameters were measured and flow cytometry analysis was performed in fresh samples within two hours of sample collection...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421266/reactive-oxygen-species-mediated-t-lymphocyte-abnormalities-in-an-iron-overloaded-mouse-model-and-iron-overloaded-patients-with-myelodysplastic-syndromes
#6
Jie Chen, Wen-Yi Lu, Ming-Feng Zhao, Xiao-Li Cao, Yan-Yu Jiang, Xin Jin, Ping Xu, Ting-Ting Yuan, Yu-Chen Zhang, Xiao Chai, Juan-Xia Meng, Qing Li, Xia Xiao, Juan Mu, De-Guan Li, Ai-Ping Qi
The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3(+) T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes...
April 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#7
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420863/changes-of-systemic-immune-response-after-stereotactic-ablative-radiotherapy-sabr-first-results-of-a-prospective-study-in-early-lung-cancer-patients
#8
Jacek Rutkowski, Tomasz Ślebioda, Zbigniew Kmieć, Renata Zaucha
INTRODUCTION    Among all lung tumors non-small cell lung cancer (NSCLC) is the most common. Conventional conservative treatment in medically inoperable patients with early stage NSCLC has a poor outcome. To improve treatment efficacy stereotactic ablative radiotherapy (SABR) has been developed to enable the delivery of high-dose radiation to the tumor.  OBJECTIVES    This prospective study was conducted to confirm the hypothesis that a sudden death of cancer cells after SABR may lead to systemic immune response changes...
April 18, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28420494/molecular-regulation-and-role-of-angiogenesis-in-reproduction
#9
REVIEW
Momchil Rizov, Petya Andreeva, Ivanka Dimova
Angiogenesis is an essential process for proper functioning of the female reproductive system and for successful pregnancy realization. The multitude of factors required for physiological angiogenesis and the complexity of regulation of their temporal-spatial activities contribute to aberrations in human fertilization and pregnancy outcomes. In this study, we reviewed the current knowledge of the temporal expression patterns, functions, and regulatory mechanisms of angiogenic factors during foliculogenesis, early implantation/placentation and embryo development, as well as recurrent spontaneous abortions...
April 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28420440/immune-response-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes-mellitus
#10
Lei Ye, Li Li, Bing Wan, Minglan Yang, Jie Hong, Weiqiong Gu, Weiqing Wang, Guang Ning
BACKGROUND: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419519/deletion-of-a-distal-rankl-gene-enhancer-delays-progression-of-atherosclerotic-plaque-calcification-in-hypercholesterolemic-mice
#11
Sohel Shamsuzzaman, Melda Onal, Hillary C St John, J Wesley Pike
Receptor activator of NF-κB ligand (RANKL) is a TNFα-like cytokine which mediates diverse physiological functions including bone remodeling and immune regulation. RANKL has been identified in atherosclerotic lesions; however, its role in atherosclerotic plaque development remains elusive. An enhancer located 75kb upstream of the murine RANKL gene's transcription start site designated D5 is important for its calciotropic hormone- and cytokine-mediated expression. Here, we determined the impact of RANKL levels in atherosclerotic plaque development in the D5 enhancer-null (D5(-/-) ) mice in an atherogenic Apoe(-/-) background fed a high-fat diet (HFD)...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416773/changes-in-t-cell-subpopulations-and-cytokine-network-during-early-period-of-ibrutinib-therapy-in-chronic-lymphocytic-leukemia-patients-the-significant-decrease-in-t-regulatory-cells-number
#12
Monika Podhorecka, Aneta Goracy, Agnieszka Szymczyk, Malgorzata Kowal, Blanca Ibanez, Olga Jankowska-Lecka, Arkadiusz Macheta, Aleksandra Nowaczynska, Elzbieta Drab-Urbanek, Sylwia Chocholska, Dariusz Jawniak, Marek Hus
B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416753/synergistic-effects-of-the-immune-checkpoint-inhibitor-ctla-4-combined-with-the-growth-inhibitor-lycorine-in-a-mouse-model-of-renal-cell-carcinoma
#13
Xiezhao Li, Peng Xu, Chongshan Wang, Naijin Xu, Abai Xu, Yawen Xu, Takuya Sadahira, Motoo Araki, Koichiro Wada, Eiji Matsuura, Masami Watanabe, Junxia Zheng, Pinghua Sun, Peng Huang, Yasutomo Nasu, Chunxiao Liu
Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation)...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413196/the-molecular-cues-regulating-immune-cell-trafficking
#14
Akira Takeda, Naoko Sasaki, Masayuki Miyasaka
Lymphocyte recirculation between the blood and the lymphoid/non-lymphoid tissues is an essential homeostatic mechanism that regulates humoral and cellular immune responses in vivo. This system promotes the encounter of naïve T and B cells with their specific cognate antigen presented by dendritic cells, and with the regulatory cells with which they need to interact to initiate, maintain, and terminate immune responses. The constitutive lymphocyte trafficking is mediated by particular types of blood vessels, including the high endothelial venules (HEVs) in lymph nodes and Peyer's patches, and the flat-walled venules in non-lymphoid tissues including the skin...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28408909/the-maternal-diet-gut-bacteria-and-bacterial-metabolites-during-pregnancy-influence-offspring-asthma
#15
REVIEW
Lawrence E K Gray, Martin O'Hely, Sarath Ranganathan, Peter David Sly, Peter Vuillermin
This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#16
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28408143/tetrandrine-potentiates-the-glucocorticoid-pharmacodynamics-via-inhibiting-p-glycoprotein-and-mitogen-activated-protein-kinase-in-mitogen-activated-human-peripheral-blood-mononuclear-cells
#17
Wencheng Xu, Kehan Meng, Yuanchao Tu, Sachiko Tanaka, Kenji Onda, Kentaro Sugiyama, Toshihiko Hirano, Haruki Yamada
Glucocorticoids play significant roles in treatments of inflammatory and autoimmune diseases. Some patients show a poor or absent response even to high doses of glucocorticoids. The purpose of this study was to explore whether tetrandrine combined with glucocorticoids could be a new treatment strategy to resolve glucocorticoids resistance. Information on glucocorticoids sensitivity was usually obtained through mitogen-activated human peripheral blood mononuclear cells in cell culture procedures. Thus, human peripheral blood mononuclear cells was chosen as a model to study the immunosuppressive effect of methylprednisolone combined with tetrandrine, including the possible action mechanisms...
April 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28406993/topical-and-systemic-immunoreaction-triggered-by-intravesical-chemotherapy-in-an-n-butyl-n-4-hydroxybutyl-nitorosamine-induced-bladder-cancer-mouse-model
#18
Shunta Hori, Makito Miyake, Yoshihiro Tatsumi, Sayuri Onishi, Yosuke Morizawa, Yasushi Nakai, Nobumichi Tanaka, Kiyohide Fujimoto
Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28405505/medi1873-a-potent-stabilized-hexameric-agonist-of-human-gitr-with-regulatory-t-cell-targeting-potential
#19
Natalie J Tigue, Lisa Bamber, John Andrews, Samantha Ireland, James Hair, Edward Carter, Sudharsan Sridharan, Jelena Jovanović, D Gareth Rees, Jeremy S Springall, Emilie Solier, Yi-Ming Li, Matthieu Chodorge, David Perez-Martinez, Daniel R Higazi, Michael Oberst, Maureen Kennedy, Chelsea M Black, Li Yan, Martin Schwickart, Shaun Maguire, Jennifer A Cann, Lolke de Haan, Lesley L Young, Tristan Vaughan, Robert W Wilkinson, Ross Stewart
Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is part of a system of signals involved in controlling T-cell activation. Targeting and agonizing GITR in mice promotes antitumor immunity by enhancing the function of effector T cells and inhibiting regulatory T cells. Here, we describe MEDI1873, a novel hexameric human GITR agonist comprising an IgG1 Fc domain, a coronin 1A trimerization domain and the human GITRL extracellular domain (ECD). MEDI1873 was optimized through systematic testing of different trimerization domains, aglycosylation of the GITRL ECD and comparison of different Fc isotypes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402334/characterization-of-c-maf-foxp3-regulatory-t-cells-induced-by-repeated-stimulation-of-antigen-presenting-b-cells
#20
Chien-Hui Chien, Hui-Chieh Yu, Szu-Ying Chen, Bor-Luen Chiang
The role of B cells in the development of CD4(+) regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(-) T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner...
April 12, 2017: Scientific Reports
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