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Nkg2d ligand

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https://www.readbyqxmd.com/read/28529563/role-of-nkg2d-in-cytokine-induced-killer-cells-against-lung-cancer
#1
Xiaowei Yin, Xuzhang Lu, Zhang Xiuwen, Zhou Min, Rong Xiao, Zhengdao Mao, Qian Zhang
It has been previously demonstrated that cytokine-induced killer (CIK) cells possess potent cytotoxicity against various cancer cells, including lung cancer cells. However, the mechanism by which CIK cells recognize lung cancer cells has not been understood. The interaction between killer cell lectin like receptor K1 (NKG2D) receptor and NKG2D ligands was demonstrated to serve an important role in target cell killing by natural killer cells. The present study investigated whether NKG2D receptor and NKG2D ligand interactions are involved in the CIK-directed killing of lung cancer cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28523761/unraveling-the-expression-of-microrna-27a-nkg2d-in-peripheral-blood-mononuclear-cells-and-natural-killer-cells-of-pediatric-systemic-lupus-erythematosus-patients
#2
Shady K Sourour, Heba R Aboelenein, Noha M Elemam, Amira K Abdelhamid, Samia Salah, Ahmed I Abdelaziz
BACKGROUND AND AIM: The activity of natural killer (NK) cells is known to be decreased in systemic lupus erythematosus (SLE) patients. Nevertheless, the exact contribution of NK cells in the pathogenesis of SLE is still inconclusive. MicroRNAs (miRNAs), are small noncoding RNA molecules that play a fundamental role in regulating NK cell function. The objective of this study was to investigate the expression of miRNAs that might potentially target an essential activating receptor, NKG2D in peripheral blood mononuclear cells (PBMCs) and NK cells of SLE patients...
May 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28500232/nkg2d-ligand-targeted-bispecific-t-cell-engagers-lead-to-robust-antitumor-activity-against-diverse-human-tumors
#3
Claire Godbersen, Tiffany A Coupet, Amelia M Huehls, Tong Zhang, Michael B Battles, Jan L Fisher, Marc S Ernstoff, Charles L Sentman
Two new bispecific T cell engaging (BiTE) molecules with specificity for NKG2D ligands were developed and functionally characterized. One, huNKG2D-OKT3, was derived from the extracellular portion of the human NKG2D receptor fused to a CD3ε binding single-chain variable fragment (scFv), known as OKT3. NKG2D has multiple ligands, including MICA, which are expressed by a variety of malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE format that targets MICA on tumor cells and CD3ε on human T cells...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499126/control-of-tumor-initiation-by-nkg2d-naturally-expressed-on-ovarian-cancer-cells
#4
Xin Cai, Andrea Caballero-Benitez, Mesfin M Gewe, Isaac C Jenkins, Charles W Drescher, Roland K Strong, Thomas Spies, Veronika Groh
Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence of its ligands for autonomous stimulation of oncogenic signaling. Previous studies raise the possibility that cancer cell NKG2D may induce high malignancy traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer as model setting, we show here that ex vivo NKG2D(+) cancer cells have stem-like capacities, and provide formal in vivo evidence linking NKG2D stimulation with the development and maintenance of these functional states...
May 9, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28455530/nkg2d-cd4-t-cells-kill-regulatory-t-cells-in-a-nkg2d-nkg2d-ligand-dependent-manner-in-systemic-lupus-erythematosus
#5
Di Yang, Zhiqiang Tian, Mengjie Zhang, Weibing Yang, Jun Tang, Yuzhang Wu, Bing Ni
Systemic lupus erythematosus (SLE) features a decreased pool of CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells. We had previously observed NKG2D(+)CD4(+) T cell expansion in contrast to a decreased pool of Treg cells in SLE patients, but whether NKG2D(+)CD4(+) T cells contribute to the decreased Treg cells remains unclear. In the present study, we found that the NKG2D(+)CD4(+) T cells efficiently killed NKG2D ligand (NKG2DL)(+) Treg cells in vitro, whereby the surviving Treg cells in SLE patients showed no detectable expression of NKG2DLs...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28452850/sunitinib-induces-nk-%C3%AE%C2%BAb-dependent-nkg2d-ligand-expression-in-nasopharyngeal-carcinoma-and-hepatoma-cells
#6
Yu-Xian Huang, Xin-Tong Chen, Kun-Yuan Guo, Yu-Hua Li, Bing-Yi Wu, Chao-Yang Song, Yan-Jie He
Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with natural killer (NK) cell adoptive transfer for the treatment in various cancers. MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28443092/disarming-cellular-alarm-systems-manipulation-of-stress-induced-nkg2d-ligands-by-human-herpesviruses
#7
REVIEW
Dominik Schmiedel, Ofer Mandelboim
The coevolution of viruses and their hosts led to the repeated emergence of cellular alert signals and viral strategies to counteract them. The herpesvirus family of viruses displays the most sophisticated repertoire of immune escape mechanisms enabling infected cells to evade immune recognition and thereby maintain infection. The herpesvirus family consists of nine viruses that are capable of infecting humans: herpes simplex virus 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), roseoloviruses (HHV-6A, HHV-6B, and HHV-7), and Kaposi's-sarcoma-associated herpesvirus (KSHV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28443091/natural-killer-group-2d-ligand-depletion-reconstitutes-natural-killer-cell-immunosurveillance-of-head-and-neck-squamous-cell-carcinoma
#8
Sandra Weil, Stefanie Memmer, Axel Lechner, Volker Huppert, Ariane Giannattasio, Tamara Becker, Andreas Müller-Runte, Karen Lampe, Dirk Beutner, Alexander Quaas, Ralf Schubert, Eva Herrmann, Alexander Steinle, Ulrike Koehl, Lutz Walter, Michael S von Bergwelt-Baildon, Joachim Koch
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28441859/-dnt-cell-inhibits-the-growth-of-pancreatic-carcinoma-via-nkg2d-and-mica-pathway-in-vivo
#9
J Chen, H Xu, X X Zhu, Y Zhao, H Z Fang, J Q Zhao
Objective: To investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class Ⅰ chain-related molecules A(MICA) on DNT cell killing pancreatic carcinoma. Methods: Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice, and then mice were randomly divided mice into 3 groups, blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28433635/prognostic-significance-and-functional-implication-of-immune-activating-receptor-nkg2d-in-gastric-cancer
#10
Fengjuan Lin, Congqi Dai, Xiaoxiao Ge, Wenbo Tang, Ying Lin, Yan Wang, Jin Li
NKG2D, an activating receptor expressed on CD8(+) T lymphocytes, serves as a co-stimulation molecule by engagement with its ligands MICA/B and ULBPs to trigger immune activation against tumors. Currently, the biological function and clinical significance of NKG2D in gastric cancer remains unexplored. The study aims to investigate the expression of NKG2D in gastric cancer in association with clinical prognosis and its biological function. Real-time PCR was used to analyze NKG2D expression in paired cancer and adjacent non-malignant tissues in 139 gastric cancer patients between 2007 and 2010 in Shanghai Cancer Center...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28423623/melanoma-associated-fibroblasts-decrease-tumor-cell-susceptibility-to-nk-cell-mediated-killing-through-matrix-metalloproteinases-secretion
#11
Linda Ziani, Thouraya Ben Safta-Saadoun, Johanne Gourbeix, Andrea Cavalcanti, Caroline Robert, Gilles Favre, Salem Chouaib, Jerome Thiery
Cancer-associated fibroblasts (CAFs) play a central role in the complex process of tumor-stroma interaction and promote tumor growth. Emerging evidences also suggest that these fibroblasts are involved in the alteration of the anti-tumor immune response by impacting several immune cell populations, especially through their secretion of pro-inflammatory and immunosuppressive factors in the tumor microenvironment. However, the underlying immuno-modulating mechanisms triggered by these fibroblasts are still only partially defined...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414183/nkg2d-a-versatile-player-in-the-immune-system
#12
REVIEW
Vedrana Jelenčić, Maja Lenartić, Felix M Wensveen, Bojan Polić
NKG2D is known as a potent activating receptor of the immune system. It is expressed on a multitude of immune cells, including NK cells and different subsets of T cells. NKG2D recognizes various MHC I-like ligands that are induced on target cells exposed to stressors such as viral infection, DNA damage and oncological transformation. NKG2D drives or facilitates cytotoxic and cytokine responses towards cells expressing its ligands to eliminate the threat. Therefore, NKG2D is usually classified as a sensor that translates cellular stress into activation signals for immune cells...
April 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28413491/upregulated-unique-long-16-binding-protein-1-detected-in-preeclamptic-placenta-affects-human-extravillous-trophoblast-cell-line-htr-8-svneo-invasion-by-modulating-the-function-of-uterine-natural-killer-cells
#13
Jing Liu, Guang Song, Xuewen Lin, Xining Pang, Tao Meng
Well-controlled trophoblast invasion at the maternal-fetal interface is crucial for normal placentation and successful pregnancy, otherwise pathological conditions of pregnancy occur, such as preeclampsia. In previous studies, it has been demonstrated that unique long 16 binding protein (ULBP)1, a ligand for the natural-killer group (NKG)2D receptor on uterine natural killer (uNK) cells, is upregulated in the placenta in patients with preeclampsia. As they are present on the majority of the decidua, uNK have an important role in pregnancy...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28404876/increasing-timp3-expression-by-hypomethylating-agents-diminishes-soluble-mica-micb-and-ulbp2-shedding-in-acute-myeloid-leukemia-facilitating-nk-cell-mediated-immune-recognition
#14
Aroa Baragaño Raneros, Alfredo Minguela Puras, Ramon M Rodriguez, Enrique Colado, Teresa Bernal, Eduardo Anguita, Adela Vasco Mogorron, Alberto Chaparro Gil, Jose Ramon Vidal-Castiñeira, Leonardo Márquez-Kisinousky, Paula Díaz Bulnes, Amelia Martinez Marin, Maria Carmen García Garay, Beatriz Suarez-Alvarez, Carlos Lopez-Larrea
Acute myeloid leukemia (AML) is a disease with great morphological and genetic heterogeneity, which complicates its prognosis and treatment. The hypomethylating agents azacitidine (Vidaza®, AZA) and decitabine (Dacogen®, DAC) have been approved for the treatment of AML patients, but their mechanisms of action are poorly understood. Natural killer (NK) cells play an important role in the recognition of AML blasts through the interaction of the activating NKG2D receptor with its ligands (NKG2DL: MICA/B and ULBPs1-3)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396673/natural-killer-group-2-member-d-nkg2d-ligands-in-hematopoietic-cell-transplantation
#15
REVIEW
Raphael Carapito, Ismail Aouadi, Wassila Ilias, Seiamak Bahram
Natural killer group 2, member D (NKG2D) is an invariant activatory receptor present on subsets of natural killer and T lymphocytes. It stimulates the cytolytic effector response upon engagement of its various stress-induced ligands NKG2D ligands (NKG2DL). Malignant transformation and conditioning treatment prior to hematopoietic cell transplantation (HCT) are stress factors leading to the activation of the NKG2D/NKG2DL signaling in clinical settings. In the context of HCT, NKG2D-bearing cells can kill both tumor and healthy cells expressing NKG2DL...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28383557/silencing-nkg2d-ligand-targeting-mirnas-enhances-natural-killer-cell-mediated-cytotoxicity-in-breast-cancer
#16
Jiaying Shen, Jie Pan, Chengyong Du, Wengong Si, Minya Yao, Liang Xu, Huilin Zheng, Mingjie Xu, Danni Chen, Shu Wang, Peifen Fu, Weimin Fan
NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DLs). NKG2DLs are expressed on malignant cells and sensitize them to early elimination by cytotoxic lymphocytes. We investigated the clinical importance of NKG2DLs and the mechanism of NKG2DL regulation in breast cancer (BC). Among the NKG2DLs MICA/B and ULBP1/2/3, the expression levels of MICA/B in BC tissues were inversely associated with the Tumor Node Metastasis stage. We first found that the high expression of MICB, but not MICA, was an independent prognostic factor for overall survival in patients with BC...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28379387/a-new-mhc-linked-susceptibility-locus-for-primary-sj%C3%A3-gren-s-syndrome-mica
#17
Raphael Carapito, Jacques-Eric Gottenberg, Irina Kotova, Meiggie Untrau, Sandra Michel, Lydie Naegely, Ismail Aouadi, Marius Kwemou, Nicodème Paul, Angélique Pichot, James Locke, Simon J Bowman, Bridget Griffiths, Kathy L Sivils, Jean Sibilia, Hidetoshi Inoko, Corinne Micelli-Richard, Gaétane Nocturne, Masao Ota, Wan-Fai Ng, Xavier Mariette, Seiamak Bahram
The association of primary Sjögren's syndrome (pSS) with Major Histocompatibility Complex (MHC) alleles is quintessential of MHC-disease associations. Indeed, although disease associations with classical HLA class I and II alleles/haplotypes are amply documented, further dissection is often prevented by the strong linkage disequilibrium across the entire MHC complex. Here we study the association of pSS, not with HLA genes, but with the non-conventional MHC encoded class I gene, MICA (MHC class I chain-related gene A)...
April 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28378389/nkg2d-stimulation-of-cd8-t-cells-during-priming-promotes-their-capacity-to-produce-cytokines-in-response-to-viral-infection-in-mice
#18
Inga Kavazović, Maja Lenartić, Vedrana Jelenčić, Slaven Jurković, Niels A W Lemmermann, Stipan Jonjić, Bojan Polić, Felix M Wensveen
Natural killer group 2 member D (NKG2D) is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ, and CD8(+) T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8(+) T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here, we studied the impact of NKG2D on effector CD8(+) T-cell formation. NKG2D deficiency that is restricted to murine CD8(+) T cells did not impair antigen-specific T-cell expansion following mouse CMV and lymphocytic choriomeningitis virus infection, but reduced their capacity to produce cytokines...
April 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28356383/vigilin-regulates-the-expression-of-the-stress-induced-ligand-micb-by-interacting-with-its-5-untranslated-region
#19
Orit Berhani, Daphna Nachmani, Rachel Yamin, Dominik Schmiedel, Yotam Bar-On, Ofer Mandelboim
NK cells are part of the innate immune system, and are able to identify and kill hazardous cells. The discrimination between normal and hazardous cells is possible due to an array of inhibitory and activating receptors. NKG2D is one of the prominent activating receptors expressed by all human NK cells. This receptor binds stress-induced ligands, including human MICA, MICB, and UL16-binding proteins 1-6. The interaction between NKG2D and its ligands facilitates the elimination of cells under cellular stress, such as tumor transformation...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#20
Daniela Ortner, Christoph H Tripp, Kerstin Komenda, Sandrine Dubrac, Bernhard Zelger, Martin Hermann, Wolfgang Doppler, Piotr Z Tymoszuk, Louis Boon, Björn E Clausen, Patrizia Stoitzner
Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin...
2017: Oncoimmunology
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