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Tim-3 NK cell

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https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#1
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by 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...
January 16, 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
#2
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 evidences 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...
December 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-co-inhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-of-systemic-sclerosis-patients
#3
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. Here, we measured the expression and function of the co-inhibitory receptors (co-IRs) PD-1, TIGIT, TIM-3, and LAG-3 in lymphocyte subsets from the peripheral blood of SSc patients. METHODS: Co-IR expression levels on immune cell subsets were analyzed using a 16-color flow cytometry panel...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29197679/recipient-t-cell-exhaustion-and-successful-adoptive-transfer-of-haploidentical-natural-killer-cells
#4
Robin L Williams, Sarah Cooley, Veronika Bachanova, Bruce R Blazar, Daniel J Weisdorf, Jeffrey S Miller, Michael R Verneris
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 persistence at D+14, but the factors influencing NK cell persistence are unknown. To address this question, patient samples from a phase I trial of NCI IL-15 in whom either did or did not show NK cell expansion were compared to healthy donor controls. Prior to lymphodepleting chemotherapy, high absolute CD3+ count was predictive of patients who failed to expand their haplo-NK cell graft...
November 29, 2017: 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
#5
Xueen Li, Bo Wang, Lintao Gu, 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...
November 21, 2017: 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
#6
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
#7
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
#8
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
#9
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
#10
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...
September 13, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28890545/tim-3-a-crucial-regulator-of-nk-cells-in-pregnancy
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28615524/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 4th 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)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585539/il-21-mediated-reversal-of-nk-cell-exhaustion-facilitates-anti-tumour-immunity-in-mhc-class-i-deficient-tumours
#16
Hyungseok Seo, Insu Jeon, Byung-Seok Kim, Myunghwan Park, Eun-Ah Bae, Boyeong Song, Choong-Hyun Koh, Kwang-Soo Shin, Il-Kyu Kim, Kiyoung Choi, Taegwon Oh, Jiyoun Min, Byung Soh Min, Yoon Dae Han, Suk-Jo Kang, Sang Joon Shin, Yeonseok Chung, Chang-Yuil Kang
During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28440449/preoperative-tim%C3%A2-3-expression-on-peripheral-nk-cells-is-correlated-with-pathologic-tnm-staging-in-colorectal-cancer
#17
Yang Wang, Jintang Sun, Wenjuan Gao, Bingfeng Song, Qianqian Shao, Lei Zhao, Yun Zhang, Qingjie Wang, Yun Zhang, Xun Qu
Previous research has indicated that T cell immunoglobulin and mucin domain 3 (Tim-3) serves an important regulatory role in lymphocytes and in several cancers. However, the association between Tim‑3 expression on various lymphocyte subsets and human colorectal cancer (CRC) has not been elucidated. The present study aimed to characterize Tim‑3 expression on peripheral lymphocytes, including cluster of differentiation CD3+CD56‑ T cells, CD3‑CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells, in patients with CRC...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28423034/elevated-frequencies-of-cd8-t-cells-expressing-pd-1-ctla-4-and-tim-3-within-tumour-from-perineural-squamous-cell-carcinoma-patients
#18
Richard Linedale, Campbell Schmidt, Brigid T King, Annabelle G Ganko, Fiona Simpson, Benedict J Panizza, Graham R Leggatt
Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas...
2017: PloS One
https://www.readbyqxmd.com/read/28373665/polyfunctional-natural-killer-cells-with-a-low-activation-profile-in-response-to-toll-like-receptor-3-activation-in-hiv-1-exposed-seronegative-subjects
#19
Josenilson F Lima, Luanda M S Oliveira, Nátalli Z Pereira, Alberto J S Duarte, Maria N Sato
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344869/il-15-tim-3-and-nk-cells-subsets-predict-responsiveness-to-anti-ctla-4-treatment-in-melanoma-patients
#20
Rossana Tallerico, Costanza M Cristiani, Elina Staaf, Cinzia Garofalo, Rosa Sottile, Mariaelena Capone, Yago Pico de Coaña, Gabriele Madonna, Eleonora Palella, Maria Wolodarski, Valentina Carannante, Domenico Mallardo, Ester Simeone, Antonio M Grimaldi, Sofia Johansson, Paolo Frumento, Elio Gulletta, Andrea Anichini, Francesco Colucci, Gennaro Ciliberto, Rolf Kiessling, Klas Kärre, Paolo A Ascierto, Ennio Carbone
Despite the success of immune checkpoint blockade in melanoma, the majority of patients do not respond. We hypothesized that the T and NK cell subset frequencies and expression levels of their receptors may predict responses and clinical outcome of anti-CTLA-4 treatment. We thus characterized the NK and T cell phenotype, as well as serum levels of several cytokines in 67 melanoma patients recruited in Italy and Sweden, using samples drawn prior to and during treatment. Survival correlated with low expression of the inhibitory receptor TIM-3 on circulating T and NK cells prior to and during treatment and with the increased frequency of mature circulating NK cells (defined as CD3(-)CD56(dim) CD16(+)) during treatment...
2017: Oncoimmunology
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