keyword
MENU ▼
Read by QxMD icon Read
search

T cell inhibitory pathway

keyword
https://www.readbyqxmd.com/read/28717244/trail-regulatory-receptors-constrain-human-hepatic-stellate-cell-apoptosis
#1
Harsimran D Singh, Itziar Otano, Krista Rombouts, Kasha P Singh, Dimitra Peppa, Upkar S Gill, Katrin Böttcher, Patrick T F Kennedy, Jude Oben, Massimo Pinzani, Henning Walczak, Giuseppe Fusai, William M C Rosenberg, Mala K Maini
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708837/extracellular-inhibitors-can-attenuate-tumorigenic-wnt-pathway-activity-in-adenomatous-polyposis-coli-mutants-predictions-of-a-validated-mathematical-model
#2
Gili Hochman, Karin Halevi-Tobias, Yuri Kogan, Zvia Agur
BACKGROUND: Despite considerable investigational efforts, no method to overcome the pathogenesis caused by loss of function (LoF) mutations in tumor suppressor genes has been successfully translated to the clinic. The most frequent LoF mutation in human cancers is Adenomatous polyposis coli (APC), causing aberrant activation of the Wnt pathway. In nearly all colon cancer tumors, the APC protein is truncated, but still retains partial binding abilities. OBJECTIVE & METHODS: Here, we tested the hypothesis that extracellular inhibitors of the Wnt pathway, although acting upstream of the APC mutation, can restore normal levels of pathway activity in colon cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28687658/the-effect-of-inhibitory-signals-on-the-priming-of-drug-hapten-specific-t-cells-that-express-distinct-v%C3%AE-receptors
#3
Andrew Gibson, Lee Faulkner, Maike Lichtenfels, Monday Ogese, Zaid Al-Attar, Ana Alfirevic, Philipp R Esser, Stefan F Martin, Munir Pirmohamed, B Kevin Park, Dean J Naisbitt
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28686966/pectolinarigenin-from-the-leaves-of-clerodendrum-volubile-shows-potent-immunomodulatory-activity-by-inhibiting-t-cell-proliferation-and-modulating-respiratory-oxidative-burst-in-phagocytes
#4
Ochuko L Erukainure, M Ahmed Mesaik, Olubunmi Atolani, Aliyu Muhammad, Chika I Chukwuma, Md Shahidul Islam
There have been increasing interest in the use of plant-derived substance as immunomodulators for the treatment and management of inflammatory ailments. Clerodendrum volubile, a leafy vegetable is known for its folkloric applications in the treatments of several inflammatory related ailments, but with little scientific evidence. This study reports the isolation, structure elucidation and in vitro immunomodulatory potentials of pectolinarigenin from C. volubile leaves. The immunomodulatory potentials of the crude methanolic extract and fractions [n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n - butanol (BuOH)] were investigated on whole blood, neutrophil and macrophage phagocytic respiratory burst using luminol-amplified chemiluminescence technique...
July 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28681958/bj-2266-ameliorates-experimental-autoimmune-encephalomyelitis-through-down-regulation-of-the-jak-stat-signaling-pathway
#5
Zhiwei You, Maheshwor Timilshina, Byeong-Seon Jeong, Jae-Hoon Chang
CD4(+) T cells differentiate into distinct effector subsets upon antigenic stimulation. Cytokines, and micro-environmental factors present during T-cell priming, direct differentiation of naïve CD4(+) T cells into pro-inflammatory Th1 and Th17 cells. From extensive screening of 2,4,5-trimethylpyridin-3-ol derivatives with various functional groups at C(6)-position, BJ-2266, a 6-thioureido-derivative, showed potent inhibitory activity on in vitro T helper (Th)-cell differentiation. This compound inhibited IFN-γ and IL-17 production from polyclonal CD4(+) T cells and ovalbumin (OVA)-specific CD4(+) T cells that were activated by T-cell receptor (TCR) engagement...
July 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28669340/oncolytic-tanapoxvirus-expressing-interleukin-2-is-capable-of-inducing-the-regression-of-human-melanoma-tumors-in-the-absence-of-t-cells
#6
Tiantian Zhang, Dennis H Kordish, Yogesh R Suryawanshi, Rob R Eversole, Steven Kohler, Charles D Mackenzie, Karim Essani
Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system. In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene...
June 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28664195/partial-exhaustion-of-cd8-t-cells-and-clinical-response-to-teplizumab-in-new-onset-type-1-diabetes
#7
S Alice Long, Jerill Thorpe, Hannah A DeBerg, Vivian Gersuk, James Eddy, Kristina M Harris, Mario Ehlers, Kevan C Herold, Gerald T Nepom, Peter S Linsley
Biologic treatment of T1D typically results in transient stabilization of C-peptide levels (a surrogate for endogenous insulin secretion) in some patients, followed by progression at the same rate as in untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody teplizumab. We identified a population of CD8 T cells that accumulated in subjects with the best response to treatment (responders) and showed that these cells phenotypically resembled exhausted T cells by expressing high levels of the transcription factor EOMES, effector molecules, and multiple inhibitory receptors (IRs), including TIGIT and KLRG1...
November 2016: Science Immunology
https://www.readbyqxmd.com/read/28657829/cd55-deficiency-early-onset-protein-losing-enteropathy-and-thrombosis
#8
Ahmet Ozen, William A Comrie, Rico C Ardy, Cecilia Domínguez Conde, Buket Dalgic, Ömer F Beser, Aaron R Morawski, Elif Karakoc-Aydiner, Engin Tutar, Safa Baris, Figen Ozcay, Nina K Serwas, Yu Zhang, Helen F Matthews, Stefania Pittaluga, Les R Folio, Aysel Unlusoy Aksu, Joshua J McElwee, Ana Krolo, Ayca Kiykim, Zeren Baris, Meltem Gulsan, Ismail Ogulur, Scott B Snapper, Roderick H J Houwen, Helen L Leavis, Deniz Ertem, Renate Kain, Sinan Sari, Tülay Erkan, Helen C Su, Kaan Boztug, Michael J Lenardo
BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance...
July 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28656682/mechanisms-of-pthrp-induced-inhibition-of-smooth-muscle-contractility-in-the-guinea-pig-gastric-antrum
#9
H Ohguchi, R Mitsui, K Imaeda, T Joh, H Hashitani
BACKGROUND: Parathyroid hormone-related protein (PTHrP) that causes hypercalcemia of malignancy appears to function as an endogenous smooth muscle relaxant. For example, PTHrP released upon bladder wall distension relaxes detrusor smooth muscle to accommodate urine. Here, we explored mechanisms underlying PTHrP-induced suppression of the smooth muscle contractility in the gastric antrum that also undergoes a passive distension. METHODS: Effects of PTHrP on phasic contractions and electrical slow waves in the antral smooth muscle of the guinea pig stomach were studied using isometric tension and intracellular microelectrode recordings, respectively...
June 28, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28654818/high-throughput-screening-of-myxoid-liposarcoma-cell-lines-survivin-is-essential-for-tumor-growth
#10
Marieke A de Graaff, Shruti Malu, Irma Guardiola, Alwine B Kruisselbrink, Yvonne de Jong, Willem E Corver, H Gelderblom, Patrick Hwu, Torsten O Nielsen, Alexander J Lazar, Neeta Somaiah, Judith V M G Bovée
Myxoid liposarcoma (MLS) is a soft tissue sarcoma characterized by a recurrent t(12;16) translocation. Although tumors are initially radio- and chemosensitive, the management of inoperable or metastatic MLS can be challenging. Therefore, our aim was to identify novel targets for systemic therapy. We performed an in vitro high-throughput drug screen using three MLS cell lines (402091, 1765092, DL-221), which were treated with 273 different drugs at four different concentrations. Cell lines and tissue microarrays were used for validation...
June 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#11
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#12
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28645613/regulation-of-testicular-steroidogenesis-by-foxa3-via-transcriptional-modulation-of-er%C3%AE-signaling-in-type-2-diabetes-mellitus-t2dm
#13
Yong Zhao, Hong-Xin Li, Ke Wang, Bin-Yuan Yan, Wei Li
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#14
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#15
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28639625/microrna-34a-dependent-regulation-of-axl-controls-the-activation-of-dendritic-cells-in-inflammatory-arthritis
#16
Mariola Kurowska-Stolarska, Stefano Alivernini, Emma Garcia Melchor, Aziza Elmesmari, Barbara Tolusso, Clare Tange, Luca Petricca, Derek S Gilchrist, Gabriele Di Sante, Chantal Keijzer, Lynn Stewart, Clara Di Mario, Vicky Morrison, James M Brewer, Duncan Porter, Simon Milling, Ronald D Baxter, David McCarey, Elisa Gremese, Greg Lemke, Gianfranco Ferraccioli, Charles McSharry, Iain B McInnes
Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance to pathogenesis by activating auto-reactive lymphocytes. Here we show that microRNA-34a provides homoeostatic control of CD1c(+) DC activation via regulation of tyrosine kinase receptor AXL, an important inhibitory DC auto-regulator. This pathway is aberrant in CD1c(+) DCs from patients with RA, with upregulation of miR-34a and lower levels of AXL compared to DC from healthy donors...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28638725/administration-of-a-vasoactive-intestinal-peptide-antagonist-enhances-the-autologous-anti-leukemia-t-cell-response-in-murine-models-of-acute-leukemia
#17
Christopher T Petersen, Jian-Ming Li, Edmund K Waller
Vasoactive intestinal peptide (VIP) is a neuroendocrine peptide hormone that has potent anti-inflammatory activities. VIP signaling through its receptor VPAC1 on T cells leads to reduced proliferation and a reduction in pro-inflammatory cytokine secretion. We report here that inhibition of the VIP pathway with a peptide antagonist significantly enhances a T-cell-dependent, autologous anti-leukemia response in murine models of acute myeloid leukemia and T lymphoblastic leukemia. Subcutaneous administration of the VIP antagonist, VIPhyb, resulted in reduced tumor burden and significantly enhanced survival (30-50% survival) over vehicle-treated controls (0-20% survival)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#18
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#19
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#20
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
keyword
keyword
115212
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"