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https://www.readbyqxmd.com/read/28802902/pseudomonas-aeruginosa-mannose-sensitive-hemagglutinin-injection-treated-cytokine-induced-killer-cells-combined-with-chemotherapy-in-the-treatment-of-malignancies
#1
Chaoqi Zhang, Zhen Zhang, Liping Wang, Jiaoling Han, Feng Li, Chunyi Shen, Hong Li, Lan Huang, Xuan Zhao, Dongli Yue, Jianmin Huang, Yan Yan, Yi Zhang
Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) injection serves as immunological adjuvant in clinical treatment of cancer patients. In present study, we investigated whether PA-MSHA injection enhanced the anti-tumor efficacy of CIK cells. Twenty patients with malignancies were enrolled in this retrospective clinical trial. They were divided into two groups: 10 patients received PA-MSHA treated CIK cells transfusion combined with chemotherapy, and other patients accepted CIK cells and chemotherapy...
August 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28801238/a-co-inhibitory-alliance-in-myeloid-leukemia-tim-3-galectin-9-complex-as-a-new-target-for-checkpoint-blockade-therapy
#2
M Alper Kursunel, Gunes Esendagli
No abstract text is available yet for this article.
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28800954/a-tim-3-oligonucleotide-aptamer-enhances-t-cell-functions-and-potentiates-tumor-immunity-in-mice
#3
Tal Gefen, Iris Castro, Darija Muharemagic, Yvonne Puplampu-Dove, Shradha Patel, Eli Gilboa
T cell immunoglobulin-3 (TIM-3) is a negative regulator of interferon-γ (IFN-γ) secreting CD4(+) T cells and CD8(+) T cytotoxic cells. Recent studies have highlighted the role of TIM-3 as an important mediator of CD8(+) T cell exhaustion in the setting of chronic viral infections and cancer. In murine tumor models, antibody blockade of TIM-3 with anti-TIM-3 antibodies as monotherapy has no or minimal antitumor activity, suggesting that TIM-3 signaling exerts an accessory or amplifying effect in keeping immune responses in check...
August 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28799242/negative-regulation-of-nlrp3-inflammasome-activation-by-tim-3-protects-against-peritonitis
#4
Wei Wang, Qingzhu Shi, Shuaijie Dou, Ge Li, Xinhui Shi, Xingwei Jiang, Zhiding Wang, Dandan Yu, Guojiang Chen, Wang Ren Xi, He Xiao, Chunmei Hou, Jiannan Feng, Beifen Shen, Yuanfang Ma, Gencheng Han
The NLRP3 inflammasome plays roles in host defense against invading pathogens and in the development of autoimmune damage. Strict regulation of these responses is important to avoid detrimental effects. Here, we demonstrate that Tim-3, an immune checkpoint inhibitor, inhibits NLRP3 inflammasome activation by damping basal and LPS-induced NF-κB-mediated upregulation of NLRP3 and IL-1β during the priming step and basal and ATP/LPS-induced ATP production, K(+) efflux, and ROS production during the activation step...
August 11, 2017: Immunology
https://www.readbyqxmd.com/read/28791012/extracellular-vesicles-transfer-the-receptor-programmed-death-1-in-rheumatoid-arthritis
#5
Stinne R Greisen, Yan Yan, Aida S Hansen, Morten T Venø, Jens R Nyengaard, Søren K Moestrup, Malene Hvid, Gordon J Freeman, Jørgen Kjems, Bent Deleuran
INTRODUCTION: Extracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28772217/interaction-between-galectin-9-tim-3-pathway-and-follicular-helper-cd4-t-cells-contributes-to-viral-persistence-in-chronic-hepatitis-c
#6
Ya Zhuo, Yi-Fu Zhang, Hong-Jie Wu, Lei Qin, Yan-Ping Wang, A-Min Liu, Xin-Hong Wang
Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4(+) T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4(+) T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28771750/comprehensive-t-cell-immunophenotyping-and-next-generation-sequencing-from-hpv-positive-and-negative-head-and-neck-squamous-cell-carcinomas
#7
Kate Poropatich, Joel Fontanarosa, Suchitra Swaminathan, Dave Dittmann, Siqi Chen, Sandeep Samant, Bin Zhang
The success of PD-1 inhibition in achieving a clinical response in a subset of HNSCC patients emphasizes the need to better understand the immunobiology of head and neck squamous cell carcinomas (HNSCC). Immunophenotyping was performed on 30 patients with HNSCC (16 HPV-positive, 14 HPV-negative) from matched tissue from the primary tumor site, locally metastatic cervical lymph nodes (LN), uninvolved local cervical LN and peripheral blood. CD4(+) and CD8(+) T cell lymphocytes obtained from tissue were analyzed for expression levels of inhibitory receptors PD-1, TIM-3 and CTLA-4...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28771603/expression-of-pd-l1-and-other-immunotherapeutic-targets-in-thymic-epithelial-tumors
#8
Kathryn C Arbour, Jarushka Naidoo, Keith E Steele, Ai Ni, Andre L Moreira, Natasha Rekhtman, Paul B Robbins, Joyson Karakunnel, Andreas Rimner, James Huang, Gregory J Riely, Matthew D Hellmann
INTRODUCTION: The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs...
2017: PloS One
https://www.readbyqxmd.com/read/28761757/mechanisms-of-action-and-rationale-for-the-use-of-checkpoint-inhibitors-in-cancer
#9
REVIEW
Clemence Granier, Eleonore De Guillebon, Charlotte Blanc, Helene Roussel, Cecile Badoual, Elia Colin, Antonin Saldmann, Alain Gey, Stephane Oudard, Eric Tartour
The large family of costimulatory molecules plays a crucial role in regulation of the immune response. These molecules modulate TCR signalling via phosphorylation cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA-4, already constitute approved targets in cancer therapy and, since 2011, have opened a new area of antitumour immunotherapy. Many antibodies targeting other inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory molecules (OX40, GITR and so on) are under evaluation...
2017: ESMO Open
https://www.readbyqxmd.com/read/28758198/mir-15a-16-deficiency-enhances-anti-tumor-immunity-of-glioma-infiltrating-cd8-t-cells-through-targeting-mtor
#10
Jiao Yang, Ronghua Liu, Yuting Deng, Jiawen Qian, Zhou Lu, Yuedi Wang, Dan Zhang, Feifei Luo, Chu Yiwei
MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act as an immune regulator in inflammatory disorders besides its aberrant expression in cancers. However, little is known about its regulation in tumor-infiltrating immune cells. In this study, using an orthotropic GL261 mouse glioma model, we found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged mice survival, which might be associated with the accumulation of tumor-infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells...
July 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28757398/high-expression-of-tim-3-and-kim-1-in-blood-and-urine-of-renal-allograft-rejection-patients
#11
Sanaz Keshavarz Shahbaz, Fatemeh Pourrezagholi, Mehri Barabadi, Farshad Foroughi, Morteza Hosseinzadeh, Pedram Ahmadpoor, Mohesn Nafar, Mir Saeed Yekaninejad, Aliakbar Amirzargar
BACKGROUND: T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG)...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28756232/tim3-galectin-9-alleviates-the-inflammation-of-tao-patients-via-suppressing-akt-nf-kb-signaling-pathway
#12
Lihua Luo, Dongmei Li, Kang Wang, Shuang Li, Jigang Yang, Chunlin Li, Wei Feng, Hong Guo
Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts...
July 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28754800/frontline-science-tim-3-mediated-dysfunctional-engulfment-of-apoptotic-cells-in-sle
#13
Di Zhao, Min Guo, Bing Liu, Qinghai Lin, Tingting Xie, Qianqian Zhang, Xiaoxia Jia, Qiang Shu, Xiaohong Liang, Lifen Gao, Chunhong Ma
T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28750861/the-tim-3-galectin-9-secretory-pathway-is-involved-in-the-immune-escape-of-human-acute-myeloid-leukemia-cells
#14
Isabel Gonçalves Silva, Inna M Yasinska, Svetlana S Sakhnevych, Walter Fiedler, Jasmin Wellbrock, Marco Bardelli, Luca Varani, Rohanah Hussain, Giuliano Siligardi, Giacomo Ceccone, Steffen M Berger, Yuri A Ushkaryov, Bernhard F Gibbs, Elizaveta Fasler-Kan, Vadim V Sumbayev
Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)-dependent manner...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#15
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#16
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
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
#17
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...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28681697/analysis-of-tim-3-as-a-therapeutic-target-in-prostate-cancer
#18
Yongrui Piao, Xuanshun Jin
Tim-3 (T-cell immunoglobulin domain and mucin domain-containing molecule 3) is a newly discovered immunomodulatory protein, which plays an important role in immunity regulation. Recent evidence suggests that Tim-3 is differentially regulated in a variety of tumors and has potential as a therapeutic target. The aim of this study was to investigate the effect of Tim-3 on the development of prostate cancer. Tim-3 expressing on peripheral CD4+ T and CD8+ T cells was analyzed by flow cytometry. The relationships between Tim-3 expression and clinicopathological features were analyzed...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#19
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#20
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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