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Tim3 TREG

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https://www.readbyqxmd.com/read/27744729/epigallocatechin-3-gallate-prevents-triptolide-induced-hepatic-injury-by-restoring-the-th17-treg-balance-in-mice
#1
Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27447564/mir-28-modulates-exhaustive-differentiation-of-t-cells-through-silencing-programmed-cell-death-1-and-regulating-cytokine-secretion
#2
Qing Li, Nathan Johnston, Xiufen Zheng, Hongmei Wang, Xusheng Zhang, Dian Gao, Weiping Min
T cell exhaustion is a state of T cell dysfunction that arises during many cancer. miRNAs are one of major gene regulators which result in translational inhibition and/or mRNA degradation. We hypothesized that miRNAs exist that can silence PD1 and act as a modulator in vitro to revert exhaustive status of T cells. We demonstrated that the exhausted T cells with inhibitory receptors (IRs) are significantly increased in the melanoma-bearing mice. Meanwhile, the differentiated miRNA profiles in PD1+ exhaustive T cells were identified using a miRNA array; 11 miRNAs were observed with significant altered levels in the exhausted T cells isolated from melanoma-bearing mice...
July 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27192116/the-ido1-selective-inhibitor-epacadostat-enhances-dendritic-cell-immunogenicity-and-lytic-ability-of-tumor-antigen-specific-t-cells
#3
Caroline Jochems, Massimo Fantini, Romaine I Fernando, Anna R Kwilas, Renee N Donahue, Lauren M Lepone, Italia Grenga, Young-Seung Kim, Martin W Brechbiel, James L Gulley, Ravi A Madan, Christopher R Heery, James W Hodge, Robert Newton, Jeffrey Schlom, Kwong Y Tsang
Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27044824/downregulation-of-il-10-secretion-by-treg-cells-in-osteoarthritis-is-associated-with-a-reduction-in-tim-3-expression
#4
Shufeng Li, Jinliang Wan, William Anderson, Huaqiang Sun, Hu Zhang, Xianbo Peng, Zhaolong Yu, Teng Wang, Xinfeng Yan, Wendy Smith
Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed...
April 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/26872697/interleukin-35-limits-anti-tumor-immunity
#5
Meghan E Turnis, Deepali V Sawant, Andrea L Szymczak-Workman, Lawrence P Andrews, Greg M Delgoffe, Hiroshi Yano, Amy J Beres, Peter Vogel, Creg J Workman, Dario A A Vignali
Regulatory T (Treg) cells pose a major barrier to effective anti-tumor immunity. Although Treg cell depletion enhances tumor rejection, the ensuing autoimmune sequelae limits its utility in the clinic and highlights the need for limiting Treg cell activity within the tumor microenvironment. Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function. Using an IL-35 reporter mouse, we observed substantial enrichment of IL-35(+) Treg cells in tumors. Neutralization with an IL-35-specific antibody or Treg cell-restricted deletion of IL-35 production limited tumor growth in multiple murine models of human cancer...
February 16, 2016: Immunity
https://www.readbyqxmd.com/read/26683225/identification-of-tim3-2-fluoro-oligonucleotide-aptamer-by-ht-selex-for-cancer-immunotherapy
#6
Sandra Hervas-Stubbs, Mario M Soldevilla, Helena Villanueva, Uxua Mancheño, Maurizio Bendandi, Fernando Pastor
TIM3 belongs to a family of receptors that are involved in T-cell exhaustion and Treg functions. The development of new therapeutic agents to block this type of receptors is opening a new avenue in cancer immunotherapy. There are currently several clinical trials ongoing to combine different immune-checkpoint blockades to improve the outcome of cancer patients. Among these combinations we should underline PD1:PDL1 axis and TIM3 blockade, which have shown very promising results in preclinical settings. Most of these types of therapeutic agents are protein cell-derived products, which, although broadly used in clinical settings, are still subject to important limitations...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/25505237/effect-of-nasopharyngeal-carcinoma-derived-exosomes-on-human-regulatory-t-cells
#7
COMPARATIVE STUDY
Dhafer Mrizak, Nathalie Martin, Clément Barjon, Anne-Sophie Jimenez-Pailhes, Rami Mustapha, Toshiro Niki, Joël Guigay, Véronique Pancré, Yvan de Launoit, Pierre Busson, Olivier Moralès, Nadira Delhem
BACKGROUND: Regulatory T cells (Treg) and tumor-exosomes are thought to play a role in preventing the rejection of malignant cells in patients bearing nasopharyngeal carcinoma (NPC). METHODS: Treg recruitment by exosomes derived from NPC cell lines (C15/C17-Exo), exosomes isolated from NPC patients' plasma (Patient-Exo), and CCL20 were tested in vitro using Boyden chamber assays and in vivo using a xenograft SCID mouse model (n = 5), both in the presence and absence of anti-CCL20 monoclonal antibodies (mAb)...
January 2015: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/25220265/intraepithelial-macrophage-infiltration-is-related-to-a-high-number-of-regulatory-t-cells-and-promotes-a-progressive-course-of-hpv-induced-vulvar-neoplasia
#8
Edith M G van Esch, Mariette I E van Poelgeest, J Baptist M Z Trimbos, Gert Jan Fleuren, Ekaterina S Jordanova, Sjoerd H van der Burg
Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages...
February 15, 2015: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/25189481/a-phase-i-ii-trial-of-belinostat-in-combination-with-cisplatin-doxorubicin-and-cyclophosphamide-in-thymic-epithelial-tumors-a-clinical-and-translational-study
#9
Anish Thomas, Arun Rajan, Eva Szabo, Yusuke Tomita, Corey A Carter, Barbara Scepura, Ariel Lopez-Chavez, Min-Jung Lee, Christophe E Redon, Ari Frosch, Cody J Peer, Yuanbin Chen, Richard Piekarz, Seth M Steinberg, Jane B Trepel, William D Figg, David S Schrump, Giuseppe Giaccone
PURPOSE: This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of a novel schedule of belinostat, a histone deacetylase inhibitor (HDAC) administered before and in combination with cisplatin (P), doxorubicin (A), and cyclophosphamide (C) in thymic epithelial tumors (TET). Antitumor activity, pharmacokinetics, and biomarkers of response were also assessed. EXPERIMENTAL DESIGN: Patients with advanced, unresectable TET received increasing doses of belinostat as a continuous intravenous infusion over 48 hours with chemotherapy in 3-week cycles...
November 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/24452537/the-phenotype-and-activation-status-of-regulatory-t-cells-during-friend-retrovirus-infection
#10
Jara J Joedicke, Kirsten K Dietze, Gennadiy Zelinskyy, Ulf Dittmer
The suppressive capacity of regulatory T cells (Tregs) has been extensively studied and is well established for many diseases. The expansion, accumulation, and activation of Tregs in viral infections are of major interest in order to find ways to alter Treg functions for therapeutic benefit. Tregs are able to dampen effector T cell responses to viral infections and thereby contribute to the establishment of a chronic infection. In the Friend retrovirus (FV) mouse model, Tregs are known to expand in all infected organs...
February 2014: Virologica Sinica
https://www.readbyqxmd.com/read/23734331/tim3-foxp3-regulatory-t-cells-are-tissue-specific-promoters-of-t-cell-dysfunction-in-cancer
#11
Kaori Sakuishi, Shin Foong Ngiow, Jenna M Sullivan, Michele W L Teng, Vijay K Kuchroo, Mark J Smyth, Ana C Anderson
T-cell immunoglobulin mucin 3 (TIM3) is an inhibitory molecule that has emerged as a key regulator of dysfunctional or exhausted CD8(+) T cells arising in chronic diseases such as cancer. In addition to exhausted CD8(+) T cells, highly suppressive regulatory T cells (Tregs) represent a significant barrier against the induction of antitumor immunity. We have found that the majority of intratumoral FOXP3(+) Tregs express TIM3. TIM3(+) Tregs co-express PD-1, are highly suppressive and comprise a specialized subset of tissue Tregs that are rarely observed in the peripheral tissues or blood of tumor-bearing mice...
April 1, 2013: Oncoimmunology
https://www.readbyqxmd.com/read/22341088/galectin-9-suppresses-th17-cell-development-in-an-il-2-dependent-but-tim-3-independent-manner
#12
Souichi Oomizu, Tomohiro Arikawa, Toshiro Niki, Takeshi Kadowaki, Masaki Ueno, Nozomu Nishi, Akira Yamauchi, Mitsuomi Hirashima
Galectin-9 (Gal-9) ameliorates autoimmune reactions by suppressing Th17 cells while augmenting Foxp3(+) regulatory T cells (Tregs). However, the exact mechanism of Gal-9-mediated immune modulation has been elusive. In a MOG-induced experimental allergic encephalomyelitis model using Gal-9(-/-) mice, we observed exacerbated inflammation and an increase in IL-17-producing Th17 cells balanced by a decrease in Foxp3+ Tregs. During in vitro Th17 skewing using TGF-β1 and IL-6, exogenous Gal-9 suppressed Th17 cell development and expanded Foxp3(+) Tregs from naïve CD4 T cells in an IL-2-dependent manner...
April 2012: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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