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Tim-3 NK cell

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https://www.readbyqxmd.com/read/29760706/complement-opsonized-hiv-1-alters-cross-talk-between-dendritic-cells-and-natural-killer-nk-cells-to-inhibit-nk-killing-and-to-upregulate-pd-1-cxcr3-and-ccr4-on-t-cells
#1
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29731749/adaptive-nkg2c-cd57-natural-killer-cell-and-tim-3-expression-during-viral-infections
#2
Hassen Kared, Serena Martelli, Shu Wen Tan, Yannick Simoni, Meng Li Chong, Siew Hwei Yap, Evan W Newell, Sylvia L F Pender, Adeeba Kamarulzaman, Reena Rajasuriar, Anis Larbi
Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection...
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
#3
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/29566059/the-immunological-effect-of-galectin-9-tim-3-pathway-after-low-dose-mifepristone-treatment-in-mice-at-14-5-day-of-pregnancy
#4
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/29399413/cellular-vaccination-of-mlh1-mice-an-immunotherapeutic-proof-of-concept-study
#5
Claudia Maletzki, Yvonne Saara Gladbach, Mohamed Hamed, Georg Fuellen, Marie-Luise Semmler, Jan Stenzel, Michael Linnebacher
Mismatch-repair deficiency (MMR-D) is closely linked to hypermutation and accordingly, high immunogenicity. MMR-D-related tumors thus constitute ideal vaccination targets for both therapeutic and prophylactic approaches. Herein, the prophylactic and therapeutic impact of a cellular vaccine on tumor growth and tumor-immune microenvironment was studied in a murine MLH1-/- knockout mouse model. Prophylactic application of the lysate (+/- CpG ODN 1826) delayed tumor development, accompanied by increased levels of circulating T cell numbers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29368793/different-aberrant-expression-pattern-of-immune-checkpoint-receptors-in-patients-with-ptcl-and-nk-t-cl
#6
Ziwei Liao, Xuewen Lv, Sichu Liu, Zifan He, Shaohua Chen, Liang Wang, Wenyu Li, Yangqiu Li
AIM: To better understand the T-cell immunodeficiency status in patients with peripheral T-cell lymphomas (PTCLs) and NK/T-cell lymphomas (NK/T-CLs), the T-cell inhibitory receptors expression pattern was investigated. METHODS: The expression levels of programmed death 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), B/T lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT) genes were detected in peripheral blood mononuclear cells (PBMCs) from patients and healthy volunteers by quantitative real-time-PCR, the correlation between different gene expression levels was analyzed...
January 25, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-therapy-synergizes-with-anti-pd-1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#7
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veera Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by the tumor suppressor gene TUSC2 (also known as FUS1 ) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras -mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
February 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29288118/statins-reduce-the-expressions-of-tim-3-on-nk-cells-and-nkt-cells-in-atherosclerosis
#8
Na Zhang, Min Zhang, Ru-Tao Liu, Peng Zhang, Chun-Lin Yang, Long-Tao Yue, Heng Li, Yong-Kang Li, Rui-Sheng Duan
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control...
February 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-coinhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-from-patients-with-systemic-sclerosis
#9
Michelle Fleury, Anna C Belkina, Elizabeth A Proctor, Christopher Zammitti, Robert W Simms, Douglas A Lauffenburger, Jennifer E Snyder-Cappione, Robert Lafyatis, Hans Dooms
OBJECTIVE: Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29197679/recipient-t-cell-exhaustion-and-successful-adoptive-transfer-of-haploidentical-natural-killer-cells
#10
Robin L Williams, Sarah Cooley, Veronika Bachanova, Bruce R Blazar, Daniel J Weisdorf, Jeffrey S Miller, Michael R Verneris
Natural killer (NK) cells mediate surveillance for malignancy. In some chemotherapy refractory myeloid leukemia patients, adoptive transfer of NK cells from haploidentical donors can induce remission. We have previously shown that remission induction is linked to NK cell persistence at day +14, but the factors influencing NK cell persistence are unknown. To address this question, patient samples from a phase I trial of National Cancer Institute (NCI) IL-15 in whom either did or did not show NK cell expansion were compared with healthy donor control subjects...
March 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29174343/tim-3-expression-predicts-the-abnormal-innate-immune-status-and-poor-prognosis-of-glioma-patients
#11
Xueen Li, Bo Wang, Lintao Gu, Jie Zhang, Xiaoyan Li, Lifen Gao, Chunhong Ma, Xiaohong Liang, Xingang Li
Malignant glioma, the most common and devastating primary brain tumor, has serious effects on human health with high risk of recurrence and short survival periods. Recently, the exploitation of immunological mechanisms shed new lights for developing novel therapeutic strategies for glioma pathogenesis. Tim-3, a member of T cell immunoglobulin and mucin domain family, has been involved in multiple diseases, including tumor, by regulating the viability and function of immunocytes. In the present study, we detected Tim-3 expression on peripheral innate immunocytes from glioma patients and analyzed their correlation with clinical indices...
January 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29089040/veritable-antiviral-capacity-of-natural-killer-cells-in-chronic-hbv-infection-an-argument-for-an-earlier-anti-virus-treatment
#12
Xiaoyan Li, Liang Zhou, Lin Gu, Yurong Gu, Lubiao Chen, Yifan Lian, Yuehua Huang
BACKGROUND: There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. METHODS: A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines...
October 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28974109/clinical-significance-of-t-cell-immunoglobulin-mucin-3-expression-on-peripheral-blood-mononuclear-cells-in-pediatric-acute-immune-thrombocytopenia
#13
Asmaa M Zahran, Mervat A M Youssef, Khalid I Elsayh, Mustafa M Embaby, Ahmad I M Ibrahim
T-cell immunoglobulin mucin 3 (TIM-3) is a transmembrane protein that plays an important role in several autoimmune diseases. The relationship between TIM-3 and excessive immune responses in immune thrombocytopenia (ITP) is still unknown. In this study, we evaluated the relationship between the expression of TIM-3 on peripheral blood mononuclear cells in patients with ITP and the disease severity. The frequency of lymphocyte and monocyte subsets and their TIM-3 expression were evaluated in patients with acute ITP (n = 45) and in healthy control (n = 20) using flow cytometry...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28951537/tim-3-signaling-in-peripheral-nk-cells-promotes-maternal-fetal-immune-tolerance-and-alleviates-pregnancy-loss
#14
Yanhong Li, Jiayuan Zhang, Di Zhang, Xiaowu Hong, Yu Tao, Songcun Wang, Yuanyuan Xu, Hailan Piao, Weijie Yin, Min Yu, Yin Zhang, Qiang Fu, Dajin Li, Xing Chang, Meirong Du
Pregnancy loss occurs in about 15% of clinically recognized pregnancies, and defective maternal-fetal immune tolerance contributes to more than 50% of these events. We found that signaling by the type I membrane protein T cell immunoglobulin and mucin-containing protein 3 (Tim-3) in natural killer (NK) cells had an essential protective role during early pregnancy. Tim-3 on peripheral NK (pNK) cells was transiently increased in abundance during the first trimester of pregnancy, which depended on interleukin-4 (IL-4)-signal transducer and activator of transcription 6 (STAT6) and progesterone signaling...
September 26, 2017: Science Signaling
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#15
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901003/expression-of-tim-3-and-lag-3-in-extranodal-nk-t-cell-lymphoma-nasal-type
#16
Yuhua Feng, Meizuo Zhong, Yiping Liu, Leyuan Wang, Youhong Tang
OBJECTIVE: To investigate the expression of TIM-3 and LAG-3 in extranodal NK/T cell lymphoma, nasal type (ENKTL), and evaluate the clinical and prognostic significance of TIM-3 and LAG-3 in ENKTL. METHODS: A total of 61 human paraffin-embedded specimens including 41 ENKTL and 20 rhinitis were involved. We performed immunohistochemistry to detect the expression of TIM-3 and LAG-3. We analyzed correlation between expression of TIM-3 and LAG-3 and clinicopathological features of ENKTL...
March 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/28890545/tim-3-a-crucial-regulator-of-nk-cells-in-pregnancy
#17
Yanhong Li, Dajin Li, Meirong Du
No abstract text is available yet for this article.
September 11, 2017: Cellular & Molecular Immunology
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
#18
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/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/28637584/decreased-tim-3-expression-of-peripheral-blood-natural-killer-cells-in-patients-with-severe-aplastic-anemia
#20
Tian Zhang, Xin Yuan, Chunyan Liu, Yi Li, Hui Liu, Lijuan Li, Kai Ding, Ting Wang, Honglei Wang, Zonghong Shao, Rong Fu
Severe aplastic anemia (SAA) is an autoimmune disease characterized by severe pancytopenia and bone marrow failure. In our previous studies, we found natural killer (NK) cells were aberrant in SAA patients. T cell immunoglobulin mucin-3 (TIM-3), an important regulator of immunity, is widely detected on NK cells and may contribute as a marker of activation and maturation of NK cells. In this study, we found that SAA untreated patients had lower TIM-3 expression on NK cells and CD56(dim) NK subsets compared with normal controls, and were correlated with the severity of pancytopenia of SAA...
August 2017: Cellular Immunology
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