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https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#1
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29649617/reversal-of-t-cell-exhaustion-by-the-first-donor-lymphocyte-infusion-is-associated-with-the-persistently-effective-anti-leukemic-responses-in-patients-with-relapsed-aml-after-allo-hsct
#2
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Donor lymphocyte infusion is an effective approach to treat acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective anti-leukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 non-relapsed AML controls after allo-HSCT and determined whether DLI exerts effective anti-leukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29626269/analysis-of-pd-1-and-tim-3-expression-on-cd4-t-cells-of-patients-with-rheumatoid-arthritis-negative-association-with-das28
#3
Zohreh Koohini, Hadi Hossein-Nataj, Maryam Mobini, Aref Hosseinian-Amiri, Alireza Rafiei, Hossein Asgarian-Omran
Expression of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and programmed cell death-1 (PD-1) was studied on CD4+ T cells of patients with rheumatoid arthritis (RA). Association of Tim-3 and PD-1 expression with disease activity of RA patients was also addressed. A total of 37 RA patients and 31 sex- and age-matched healthy controls were included in this study. Disease activity of RA patients was determined by Disease Activity Score of 28 joints scoring system (DAS28). A three-color flow cytometry method was applied to determine the frequency of Tim-3+ /PD-1+ /CD4+ T cells...
April 7, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29625896/co-inhibitory-molecule-b7-superfamily-member-1-expressed-by-tumor-infiltrating-myeloid-cells-induces-dysfunction-of-anti-tumor-cd8-t-cells
#4
Jing Li, Younghee Lee, Yanjian Li, Yu Jiang, Huiping Lu, Wenjuan Zang, Xiaohong Zhao, Liguo Liu, Yang Chen, Haidong Tan, Zhiying Yang, Michael Q Zhang, Tak W Mak, Ling Ni, Chen Dong
The molecular mechanisms whereby CD8+ T cells become "exhausted" in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8+ T cell dysfunction...
March 29, 2018: Immunity
https://www.readbyqxmd.com/read/29625390/dysfunction-of-regulatory-t-cells-in-patients-with-ankylosing-spondylitis-is-associated-with-a-loss-of-tim-3
#5
Mingfei Wang, Chengyi Liu, Allen Bond, Jun Yang, Xu Zhou, Jian Wang, Bin Ji
An expansion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) was observed. However, AS patients continue to exhibit aberrant inflammation. In this study, we collected PBMCs from 26 AS patients and 26 healthy controls, and investigated the functional capacity of Treg cells from these subjects. In AS patients, the frequency of CD4+ CD25+ Foxp3+ CD127- Treg cells was slightly increased compared to healthy controls, but the level of Foxp3 MFI in AS patient CD4+ CD25+ Foxp3+ CD127- Treg cells was significantly lower than that in healthy control CD4+ CD25+ Foxp3+ CD127- Treg cells...
April 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29616115/expression-of-multiple-immune-checkpoint-molecules-on-t-cells-in-malignant-ascites-from-epithelial-ovarian-carcinoma
#6
Yuichi Imai, Kosei Hasegawa, Hirokazu Matsushita, Nao Fujieda, Sho Sato, Etsuko Miyagi, Kazuhiro Kakimi, Keiichi Fujiwara
Expression of immune checkpoint molecules, including programmed cell death protein-1 (PD-1), has been reported on T cells in various types of cancer. However, the expression status of these molecules in the tumor microenvironment of epithelial ovarian cancer (EOC) has not yet been studied. A total of 54 cases of malignant ascites from patients with EOC were analyzed in the present study. The expression of PD-1, lymphocyte-activation gene-3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and B and T lymphocyte attenuator (BTLA) on cluster of differentiation (CD)4+ and CD8+ T cells in malignant EOC ascites were investigated using multicolor flow cytometric analysis...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29616020/hyper-expression-of-pd-1-is-associated-with-the-levels-of-exhausted-and-dysfunctional-phenotypes-of-circulating-cd161-tcr-iv%C3%AE-7-2-mucosal-associated-invariant-t-cells-in-chronic-hepatitis-b-virus-infection
#7
Yean K Yong, Alireza Saeidi, Hong Y Tan, Mohamed Rosmawati, Philip F Enström, Rami Al Batran, V Vasuki, Indranil Chattopadhyay, Amudhan Murugesan, Ramachandran Vignesh, Adeeba Kamarulzaman, Jayakumar Rajarajeswaran, Abdul W Ansari, Jamuna Vadivelu, James E Ussher, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Mucosal-associated invariant T (MAIT) cells, defined as CD161++ TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+ CD161++ TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615398/il-21-therapy-combined-with-pd-1-and-tim-3-blockade-provides-enhanced-nk-cell-antitumor-activity-against-mhc-class-i-deficient-tumors
#8
Hyungseok Seo, Byung-Seok Kim, Eun-Ah Bae, Byung Soh MIn, Yoon Dae Han, Sang Joon Shin, Chang-Yuil Kang
Increased expression of co-inhibitory molecules such as PD-1 and Tim-3 on NK cells has been demonstrated in advanced cancer patients who harbor MHC class I-deficient tumors. However, even in preclinical models, the antitumor effects of checkpoint blockade on NK cells have not been clearly elucidated. Here, we show that anti-PD-1/anti-Tim-3 treatment suppressed tumor progression in mice bearing MHC class I-deficient tumors, and the suppression was further enhanced by recombinant IL21(rIL21) treatments through an NK cell-dependent mechanism...
April 3, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29607331/receptors-that-inhibit-macrophage-activation-mechanisms-and-signals-of-regulation-and-tolerance
#9
REVIEW
Ranferi Ocaña-Guzman, Luis Vázquez-Bolaños, Isabel Sada-Ovalle
A variety of receptors perform the function of attenuating or inhibiting activation of cells in which they are expressed. Examples of these kinds of receptors include TIM-3 and PD-1, among others that have been widely studied in cells of lymphoid origin and, though to a lesser degree, in other cell lines. Today, several studies describe the function of these molecules as part of the diverse mechanisms of immune tolerance that exist in the immune system. This review analyzes the function of some of these proteins in monocytes and macrophages and as well as their participation as inhibitory molecules or elements of immunological tolerance that also act in innate defense mechanisms...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#10
Yong Xu, Zehua Wang, Xianhong Du, Yuan Liu, Xiaojia Song, Tixiao Wang, Siyu Tan, Xiaohong Liang, Lifen Gao, Chunhong Ma
Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29597250/expression-of-tim-3-on-plasmacytoid-dendritic-cells-as-a-predictive-biomarker-of-decline-in-hiv-1-rna-level-during-art
#11
Albert Font-Haro, Vaclav Janovec, Tomas Hofman, Ladislav Machala, David Jilich, Zora Melkova, Jan Weber, Katerina Trejbalova, Ivan Hirsch
Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fcγ receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-naïve HIV-1-infected individuals before initiation of ART when compared to healthy donors...
March 28, 2018: Viruses
https://www.readbyqxmd.com/read/29576222/blocking-tim-3-or-and-pd-1-reverses-dysfunction-of-tumor-infiltrating-lymphocytes-in-hbv-related-hepatocellular-carcinoma
#12
Furong Liu, Gucheng Zeng, Shaotang Zhou, Xiaoshun He, Nianfeng Sun, Xiaofeng Zhu, Anbin Hu
BACKGROUND: The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. METHODS: Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study...
March 22, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29570768/tim-3-exacerbates-kidney-ischemia-reperfusion-injury-through-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-and-an-nlrc4-inflammasome-activation
#13
Yunshan Guo, Jing Zhang, Xingqiang Lai, Miaojuan Chen, Yunshan Guo
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) as a member of immunoglobulin superfamily, has been shown to play a crucial role in host adaptive immunity and tolerance. However, its role in kidney ischemia-reperfusion injury (IRI) remains unknown. In this study, we investigated the role and mechanism of Tim-3 signaling after kidney IRI. In an established murine model of kidney IRI, we found that Tim-3 expression is enhanced on monocytes/macrophages. Anti-Tim-3 Ab RMT3-23 ameliorates biochemical and histologic kidney injury, reduces apoptosis, decreases macrophage infiltration and cytokine production in ischemic kidneys...
March 23, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29566059/the-immunological-effect-of-galectin-9-tim-3-pathway-after-low-dose-mifepristone-treatment-in-mice-at-14-5-day-of-pregnancy
#14
Adrienn Lajko, Matyas Meggyes, Beata Polgar, Laszlo Szereday
The abortifacient Mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first and second trimester of pregnancy although its precise mechanism of action is not well understood. The main objective of this study was to investigate the impact of low dose Mifepristone administration on placental Galectin-9 (Gal-9) expression, as well as its effect on the cell surface expression of Gal-9, TIM-3 and CD107a molecules by different T and NK cell subsets...
2018: PloS One
https://www.readbyqxmd.com/read/29560265/immune-regulation-by-tim-3
#15
REVIEW
Hridesh Banerjee, Lawrence P Kane
T-cell immunoglobulin and mucin domain 3 (Tim-3) is a transmembrane protein that in both mice and humans has been shown to possess various functions in a context-dependent manner. Thus, Tim-3 has been associated with both inhibitory and co-stimulatory function, depending in part on the specific cell type and immune response course. Though originally described on T cells, Tim-3 is now known to be expressed by both lymphoid and non-lymphoid cells within the immune system and even by non-immune cells. In addition, though widely thought of as a negative regulator of immunity, Tim-3 has been shown in more recent studies to have a positive function on both myeloid and lymphoid cells, including T cells...
2018: F1000Research
https://www.readbyqxmd.com/read/29555909/differential-expression-pattern-of-co-inhibitory-molecules-on-cd4-t-cells-in-uncomplicated-versus-complicated-malaria
#16
Annemieke Abel, Christiane Steeg, Francis Aminkiah, Otchere Addai-Mensah, Marylyn Addo, Nicola Gagliani, Christian Casar, Denis Dekugmen Yar, Ellis Owusu-Dabo, Thomas Jacobs, Maria Sophia Mackroth
The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29553498/multiplexed-immunofluorescence-analysis-and-quantification-of-intratumoral-pd-1-tim-3-cd8-t-cells
#17
Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29551917/on-the-significance-of-tim-3-expression-in-pancreatic-cancer
#18
Pu-Ji Peng, Ya Li, Shuang Sun
Objective: We aim to explore the connection between Tim-3 expression in both cancerous pancreatic and pericarcinous tissues and the clinicopathological features of pancreatic cancer. We will also preliminarily assess the role and significance of Tim-3 in the diagnosis, treatment, and prognosis of pancreatic cancer. Methods: Cancerous pancreatic and pericarcinous tissues from 50 patients with pancreatic cancer and six healthy pancreatic tissues were collected from the pathological specimens of traumatic patients to distinguish Tim-3 expression using immunohistochemistry...
December 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29547109/-tim-3-a-novel-biomarker-and-therapeutic-target-in-oncology
#19
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#20
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
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