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https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#1
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28122327/dual-roles-for-regulatory-t-cell-depletion-and-co-stimulatory-signaling-in-agonistic-gitr-targeting-for-tumor-immunotherapy
#2
Ashley Mahne, Smita Mauze, Barbara Joyce-Shaikh, Jane Xia, Edward Bowman, Amy Beebe, Daniel Cua, Renu Jain
Agonistic monoclonal antibodies (mAb) targeting the T cell receptor co-regulatory molecule GITR exert potent therapeutic activities in preclinical tumor models. Although anti-GITR mAb are thought to act by depleting and destabilizing the intratumoral T regulatory cell (Treg) population, the precise mechanism of action is obscure. Here we addressed this issue using a Treg fate-mapping approach, which revealed that Treg loss was primarily due to cell depletion, with minimal evidence of Treg conversion to a non-Foxp3-expressing population...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#3
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28101786/evaluation-of-t-regulatory-lymphocytes-transcription-factors-in-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp-patients
#4
Sanaz Ahmadi Ghezeldasht, Hamed Sadeghian, Mahmoud Reza Azarpazhooh, Seyyed Ali Akbar Shamsian, Houshang Rafatpanah, Mahmood Mahmoodi, Seyyed Abdolrahim Rezaee
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4(+)CD25(+) T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry...
January 18, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#5
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27942984/lps-treated-bone-marrow-derived-dendritic-cells-induce-immune-tolerance-through-modulating-differentiation-of-cd4-regulatory-t-cell-subpopulations-mediated-by-3g11-and-cd127
#6
Fang Zhou, Guang-Xian Zhang, Abdolmohamad Rostami
Intravenous transfer of LPS-treated bone marrow-derived dendritic cells blocks development of autoimmunity induced by CD4(+) T cells in vivo. However, cellular mechanisms of dendritic cell-mediated immune tolerance have not yet been fully elucidated. Here, we report that there are two new subpopulations of CD4(+)CD25(+)FoxP3(+)GITR(+) regulatory T cells (CD127(+)3G11(+) and CD127(+)3G11(-) cells). LPS-treated dendritic cells facilitate development of CD4(+)CD127(+)3G11(-) regulatory T cells but inhibit that of CD4(+)CD127(+)3G11(+) regulatory T cells...
December 12, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#7
Chun-Hao Lu, Cheng-Jang Wu, Cheng-Chi Chan, Duc T Nguyen, Kuo-Ray Lin, Syh-Jae Lin, Li-Chen Chen, Jeffrey Jong-Yong Yen, Ming-Ling Kuo
The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4(+) regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4(+)CD25(h)FOXP3(+) T cell induction from human CD4(+)CD25(-) T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27872515/therapeutic-treatment-of-arthritic-mice-with-15-deoxy-%C3%AE-12-14-prostaglandin-j2-15d-pgj2-ameliorates-disease-through-the-suppression-of-th17-cells-and-the-induction-of-cd4-cd25-foxp3-cells
#8
Vanessa Carregaro, Marcelo H Napimoga, Raphael S Peres, Luciana Benevides, Laís Amorim Sacramento, Larissa G Pinto, Renata Grespan, Thiago M Cunha, João Santana da Silva, Fernando Q Cunha
The prostaglandin, 15-deoxy Δ(12,14)-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27859672/immune-activation-and-regulation-related-patterns-in-stable-hand-transplant-recipients
#9
Dorota Kamińska, Katarzyna Kościelska-Kasprzak, Magdalena Krajewska, Adam Chełmoński, Jerzy Jabłecki, Marcelina Żabińska, Marta Myszka, Mirosław Banasik, Maria Boratyńska, Agnieszka Gomółkiewicz, Piotr Dzięgiel, Marian Klinger
We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations...
November 9, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27822377/erratum-to-agonist-anti-gitr-monoclonal-antibody-and-stereotactic-radiation-induce-immune-mediated-survival-advantage-in-murine-intracranial-glioma
#10
Mira A Patel, Jennifer E Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M Kochel, Brian Francica, Thomas R Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C Jackson, Christina Jackson, Xiaobu Ye, Phuoc T Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G Drake, Drew M Pardoll, Michael Lim
[This corrects the article DOI: 10.1186/s40425-016-0132-2.].
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27793666/characterization-of-%C3%AE-%C3%AE-regulatory-t-cells-from-peripheral-blood-in-patients-with-multiple-myeloma
#11
M A Yongyong, Huyi Lei, Jie Tan, Xuan Li, Xiuli Wu, Qifa Liu
γδ regulatory T cells are able to inhibit the activation and function of T cells involved in antigen-specific immune responses. This study aimed to investigate the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). We measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts...
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27777979/the-head-and-neck-cancer-immune-landscape-and-its-immunotherapeutic-implications
#12
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27757308/chemo-immunotherapy-mediates-durable-cure-of-orthotopic-kras-g12d-p53-pancreatic-ductal-adenocarcinoma
#13
Vanaja Konduri, Dali Li, Matthew M Halpert, Dan Liang, Zhengdong Liang, Yunyu Chen, William E Fisher, Silke Paust, Jonathan M Levitt, Qizhi Cathy Yao, William K Decker
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras(G12D)/p53(-/-) PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (TH1) immunity...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27734112/anti-gitr-therapy-promotes-immunity-against-malignant-glioma-in-a-murine-model
#14
Jason Miska, Aida Rashidi, Alan L Chang, Megan E Muroski, Yu Han, Lingjiao Zhang, Maciej S Lesniak
Regulatory T cells (Tregs) are potently immunosuppressive cells that accumulate within the glioma microenvironment. The reduction in their function and/or trafficking has been previously shown to enhance survival in preclinical models of glioma. Glucocorticoid-induced TNFR-related protein (GITR) is a tumor necrosis factor superfamily receptor enriched on Tregs that has shown promise as a target for immunotherapy. An agonistic antibody against GITR has been demonstrated to inhibit Tregs in a number of models and has only been recently addressed in glioma...
December 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27720959/tgf-%C3%AE-1-and-contact-mediated-suppression-by-cd4-cd25-cd127-t-regulatory-cells-of-patients-with-self-limiting-hepatitis-e
#15
Sanjay B Rathod, Anuradha S Tripathy
BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute viral infections is limited. Having established that the Tregs in self-limiting hepatitis E infection are elevated and functional, this study has focused on characterizing the specificity, phenotypes and identifying the molecules or factors responsible for enhancement of Treg cells and abrogation of Treg-mediated suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency, subset analysis and expression of surface and intracellular markers on Tregs and CFSE based functional analysis by flow cytometry (b) key cytokines quantification by multiplex (c) suppressive functional assay in the presence of anti-TGF-β1 or anti-IL-10 or both antibodies or Transwell insert or in combination were performed on samples from 58 acute patients (AVH-E), 45 recovered individuals from hepatitis E and 55 controls...
December 2016: Human Immunology
https://www.readbyqxmd.com/read/27649551/ipilimumab-with-stereotactic-ablative-radiation-therapy-phase-i-results-and-immunologic-correlates-from-peripheral-t-cells
#16
Chad Tang, James W Welsh, Patricia de Groot, Erminia Massarelli, Joe Y Chang, Kenneth R Hess, Sreyashi Basu, Michael A Curran, Maria E Cabanillas, Vivek Subbiah, Siqing Fu, Apostolia M Tsimberidou, Daniel Karp, Daniel R Gomez, Adi Diab, Ritsuko Komaki, John V Heymach, Padmanee Sharma, Aung Naing, David S Hong
PURPOSE: Little prospective data is available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiation therapy (SABR) with ipilimumab. EXPERIMENTAL DESIGN: SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to 5 treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver...
September 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27621810/combination-treatment-with-fingolimod-and-a-pathogenic-antigen-prevents-relapse-of-glucose-6-phosphate-isomerase-peptide-induced-arthritis
#17
Yuya Yoshida, Norihisa Mikami, Yuki Matsushima, Mai Miyawaki, Hiroki Endo, Rie Banno, Takumi Tsuji, Tetsuro Fujita, Takeyuki Kohno
INTRODUCTION: Combination treatment with fingolimod (FTY720) plus pathogenic antigen is thought to prevent glucose-6-phosphate isomerase (GPI)325-339-induced arthritis progression by effective induction of immune tolerance. Here, we examined the efficacy of this combination treatment on remission maintenance. METHODS: GPI325-339-induced arthritis mice were treated for 5 days with FTY720 (1.0 mg/kg, p.o.) alone, GPI325-339 (10 μg/mouse, i.v.) alone, or with the FTY720 plus GPI325-339 combination...
September 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27618667/amelioration-of-experimental-colitis-after-short-term-therapy-with-glucocorticoid-and-its-relationship-to-the-induction-of-different-regulatory-markers
#18
Helioswilton Sales-Campos, Patrícia R de Souza, Paulo J Basso, Viviani Nardini, Angelica Silva, Fernanda Banquieri, Vanessa B F Alves, Javier E L Chica, Auro Nomizo, Cristina R B Cardoso
The clinical benefits of short-term therapy with glucocorticoids (GC) in patients with inflammatory bowel disease (IBD) are widely known. However, the effects of this treatment towards the re-establishment of the regulatory network in IBD are not fully explored. We have evaluated the immunological effects of the abbreviated GC therapy in experimental colitis induced by 3% dextran sulphate sodium in C57BL/6 mice. Treatment with GC improved disease outcome, constrained circulating leucocytes and ameliorated intestinal inflammation...
January 2017: Immunology
https://www.readbyqxmd.com/read/27608299/the-tyrosine-kinase-inhibitor-tyrphostin-ag126-reduces-activation-of-inflammatory-cells-and-increases-foxp3-regulatory-t-cells-during-pathogenesis-of-rheumatoid-arthritis
#19
Sheikh Fayaz Ahmad, Mushtaq Ahmad Ansari, Ahmed Nadeem, Khairy M A Zoheir, Saleh A Bakheet, Othman A Al-Shabanah, Ammar Cherkess Al Rikabi, Sabry M Attia
Protein tyrosine kinases are key mediators of the signal transduction cascades that control expression of many genes involved in the induction of inflammation caused by arthritis. Here we investigate the effect of the tyrosine kinase inhibitor tyrphostin AG126 on a mouse model of adjuvant-induced arthritis (AIA). We report that when given at 5mg/kg i.p. every 48h from days 0-21, AG126 exerts potent anti-arthritic effects. Further, we investigated the role of AG126 on the key mediators of arthritic inflammation, namely, edema, arthritic score, presence of immunophenotypes including Foxp3(+), CD4(+)Foxp3(+), and CD25(+)Foxp3(+) T regulatory (Treg) cells, as well as pro- and anti-inflammatory mediators...
October 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27591414/rationale-for-anti-gitr-cancer-immunotherapy
#20
Deborah A Knee, Becker Hewes, Jennifer L Brogdon
Over the past decade, our understanding of cancer immunotherapy has evolved from assessing peripheral responses in the blood to monitoring changes in the tumour microenvironment. Both preclinical and clinical experience has taught us that modulation of the tumour microenvironment has significant implications to generating robust antitumour immunity. Clinical benefit has been well documented to correlate with a tumour microenvironment that contains a dense infiltration of CD8(+)CD45RO(+) T effectors and a high ratio of CD8(+) T cells to FoxP3(+) regulatory T cells (Tregs)...
November 2016: European Journal of Cancer
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