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https://www.readbyqxmd.com/read/28224733/nk1-1-cd4-nkg2d-t-cells-suppress-dss-induced-colitis-in-mice-through-production-of-tgf-%C3%AE
#1
Xingxing Qian, Chunxia Hu, Sen Han, Zhijie Lin, Weiming Xiao, Yanbing Ding, Yu Zhang, Li Qian, Xiaoqing Jia, Guoqiang Zhu, Weijuan Gong
CD4(+) NKG2D(+) T cells are associated with tumour, infection and autoimmune diseases. Some CD4(+) NKG2D(+) T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4(+) NKG2D(+) T cells were further classified into NK1.1(-) CD4(+) NKG2D(+) and NK1.1(+) CD4(+) NKG2D(+) subpopulations. The frequency of NK1.1(-) CD4(+) NKG2D(+) cells decreased in inflamed colons, whereas more NK1.1(+) CD4(+) NKG2D(+) cells infiltrated into colons of mice with DSS-induced colitis...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28223394/primary-adrenal-insufficiency-is-associated-with-impaired-natural-killer-cell-function-a-potential-link-to-increased-mortality
#2
Irina Bancos, Jon Hazeldine, Vasileios Chortis, Peter Hampson, Angela E Taylor, Janet M Lord, Wiebke Arlt
OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection...
April 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28223282/induction-of-nkg2d-ligands-on-solid-tumors-requires-tumor-specific-cd8-t-cells-and-histone-acetyltransferases
#3
Jiemiao Hu, Chantale Bernatchez, Liangfang Zhang, Xueqing Xia, Eugenie S Kleinerman, Mien-Chie Hung, Patrick Hwu, Shulin Li
NKG2D-mediated immune surveillance is crucial for inhibiting tumor growth and metastases. Malignant tumor cells often downregulate NKG2D ligands to escape from immune surveillance. High-profile studies have shown that restoring NKG2D ligand expression via genetic engineering inhibits tumor formation and progression. However, no effective in vivo approaches are available to restore these ligands across different types of solid tumors, because the classic stress signal-dependent induction of this ligand in vitro is transient and has rarely been duplicated in solid tumors in vivo We found that co-administration of an immune stimulatory signal (interleukin-12) and chemotherapy (doxorubicin) restored the NKG2D ligand Rae-1 in multiple tumor types, including a human tumor model...
February 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28220815/cbx3-hp1%C3%AE-deficiency-confers-enhanced-tumor-killing-capacity-on-cd8-t-cells
#4
Michael Sun, Ngoc Ha, Duc-Hung Pham, Megan Frederick, Bandana Sharma, Chie Naruse, Masahide Asano, Matthew E Pipkin, Rani E George, To-Ha Thai
Cbx3/HP1γ is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8(+) T cells, Cbx3/HP1γ insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8(+) T cells, there is an increase of CD8(+) effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a decrease in CD4(+) CD25(+) FOXP3(+) regulatory T cells (Treg cells) as well as CD25(+) CD4(+) T cells expressing the inhibitory receptor CTLA4...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218426/dkk3-attenuates-the-cytotoxic-effect-of-natural-killer-cells-on-cd133-gastric-cancer-cells
#5
Pu Xia, Xiao-Yan Xu
Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28203118/human-u87-glioblastoma-cells-with-stemness-features-display-enhanced-sensitivity-to-natural-killer-cell-cytotoxicity-through-altered-expression-of-nkg2d-ligand
#6
Se-Jeong Oh, Jung-In Yang, Ok Kim, Eun-Jung Ahn, Woo Dae Kang, Jae-Hyuk Lee, Kyung-Sub Moon, Kyung-Hwa Lee, Duck Cho
BACKGROUND: Glioblastoma (GBM) is one of the most lethal tumors with a poor prognosis. Its inevitable recurrence is frequently explained by the presence of cancer stem cells. We aimed to show that human GBM cells with stemness features are more sensitive to natural killer (NK) cells than GBM cells without stemness characteristics. METHODS: Natural killer cell cytotoxicity was measured using flow cytometry in neurosphere-forming U87 GBM cells cultured with neurobasal media (NBE condition) and compared with that in serum-cultured U87 GBM cells (serum condition)...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#7
Alessandra Soriani, Cristiana Borrelli, Biancamaria Ricci, Rosa Molfetta, Alessandra Zingoni, Cinzia Fionda, Silvia Carnevale, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Giuseppe La Regina, Erica Di Cesare, Patrizia Lavia, Romano Silvestri, Rossella Paolini, Marco Cippitelli, Angela Santoni
The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28191644/nk-cell-receptors-nkp46-and-ncr1-control-human-metapneumovirus-infection
#8
Mohammad Diab, Ariella Glasner, Batya Issacson, Yotam Bar-On, Yaron Drori, Rachel Yamin, Alexandra Duev-Cohen, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Stipan Jonjic, Eran Bacharach, Ofer Mandelboim
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46 activating receptor and its mouse orthologue Ncr1, both members of the NCR family, recognized an unknown ligand expressed by HMPV infected human cells...
February 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28184969/augmented-anti-tumor-activity-of-nk-92-cells-expressing-chimeric-receptors-of-tgf-%C3%AE-r-ii-and-nkg2d
#9
Zhongjuan Wang, Linghua Guo, Yuan Song, Yinsheng Zhang, Dandan Lin, Bo Hu, Yu Mei, Dedy Sandikin, Haiyan Liu
The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor)...
February 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28177768/ethanol-dependent-expression-of-the-nkg2d-ligands-mica-b-in-human-cell-lines-and-leukocytes
#10
Maria A Streltsova, Anna V Klinkova, Anastasia A Kuchukova, Andrey Y Kadin, Leonid M Kanevskiy, Elena I Kovalenko
Alcohol consumption affects human immune system, causing a variety of disorders. However, the mechanisms of development of these alterations are not fully understood. We hypothesized that ethanol may influence the expression of MICA and MICB, stress-induced molecules capable to regulate activity of cytotoxic lymphocytes through the interaction with receptor NKG2D, which substantially affects the functionality of cellular immunity. We analyzed effects of ethanol on MICA/B expression in tumor cell lines and human leukocytes...
November 2, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28169232/membrane-bound-versus-soluble-major-histocompatibility-complex-class-i-related-chain-a-and-major-histocompatibility-complex-class-i-related-chain-b-differential-expression-mechanisms-of-tumor-eradication-versus-evasion-and-current-drug-development-strategies
#11
REVIEW
P K Suresh
Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28165192/the-tgf-%C3%AE-induced-up-regulation-of-nkg2dls-requires-akt-gsk-3%C3%AE-mediated-stabilization-of-sp1
#12
Xiao-Hui Chen, Lin-Lin Lu, Hong-Peng Ke, Zong-Cai Liu, Hai-Fang Wang, Wei Wei, Yi-Fei Qi, Hong-Sheng Wang, Shao-Hui Cai, Jun Du
Natural killer (NK) cells play an important role in preventing cancer development. NK group 2 member D (NKG2D) is an activating receptor expressed in the membrane of NK cells. Tumour cells expressing NKG2DL become susceptible to an immune-dependent rejection mainly mediated by NK cells. The paradoxical roles of transforming growth factor beta (TGF-β) in regulation of NKG2DL are presented in many studies, but the mechanism is unclear. In this study, we showed that TGF-β up-regulated the expression of NKG2DLs in both PC3 and HepG2 cells...
February 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28159927/decreased-expression-of-the-nkg2d-ligand-ulbp4-may-be-an-indicator-of-poor-prognosis-in-patients-with-nasopharyngeal-carcinoma
#13
Yuanji Xu, Lin Zhou, Jingfeng Zong, Yunbin Ye, Gang Chen, Yanping Chen, Xuehong Liao, Qiaojuan Guo, Sufang Qiu, Shaojun Lin, Honglin Chen, Jianji Pan
U16-binding protein 4 (ULBP4), a human ligand for natural killer group 2, member D (NKG2D) receptor on NK cells and subsets of T cells, is thought to activate anticancer immune responses. However, the expression pattern and prognostic effect of ULBP4 in nasopharyngeal carcinoma (NPC) has not been investigated. We first compared ULBP4 expression between archival 15 NPC tissues and 8 normal nasopharynx (NP) tissues using qPCR. Then ULBP4 expression among 111 NPC specimens was validated on immunohistochemical examination...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28153802/impairment-of-peripheral-vdelta2-t-cells-in-human-cystic-echinococcosis
#14
Hao Wang, Ming Li, Xiaoxia Zhang, Fang He, Shengbin Zhang, Jiaqing Zhao
Cystic echinococcosis (CE) induced by metacestodes (larval stages) of Echinococcus granulosus (E.granulosus) represents a severe endemic disease worldwide. Gamma delta (γδ) T cells, one of innate immune cells, play pivotal role in pathogenic infections. However, whether γδ T cells are involved in CE remains unclear. This study firstly investigated the role of peripheral γδ T cells in CE. The results showed that the percentage of peripheral γδ T cells from CE patients was decreased, compared with healthy controls (HC) (p < 0...
January 31, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28143936/ebi3-regulates-the-nk-cell-response-to-mouse-cytomegalovirus-infection
#15
Helle Jensen, Shih-Yu Chen, Lasse Folkersen, Garry P Nolan, Lewis L Lanier
Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3(-/-)) C57BL/6 (B6) mice during MCMV infection...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28130828/the-effect-of-echinococcus-granulosus-on-spleen-cells-and-tgf-%C3%AE-expression-in-the-peripheral-blood-of-balb-c-mice
#16
REVIEW
Shuanghong Yin, Xiaolin Chen, Junbo Zhang, Fangjie Xu, Hairui Fang, Jun Hou, Xuyong Zhang, Xiangwei Wu, Xueling Chen
Cystic echinococcosis (CE) caused by the cestode Echinococcus granulosus (E. granulosus) is a zoonotic parasitic disease. The effective immune evasion mechanisms of E. granulosus allow it to parasitise its hosts. However, the status of the innate and adaptive immune cells and their contributions to E. granulosus progression remain poorly understood. In this study, We aimed to determine the impact of E. granulosus infection on T cells, NK cell responses and TGF-β expression during the early infection phase in BALB/c mice...
January 28, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28128200/the-immunoreceptor-nkg2d-promotes-tumour-growth-in-a-model-of-hepatocellular-carcinoma
#17
Sam Sheppard, Joana Guedes, Anna Mroz, Anastasia-Maria Zavitsanou, Hiromi Kudo, Stephen M Rothery, Panagiotis Angelopoulos, Robert Goldin, Nadia Guerra
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8(+)T cells to the liver and exacerbated pro-inflammatory milieu...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28123600/activation-or-suppression-of-the-immune-response-mediators-in-biliary-tract-cancer-btc-patients-a-systematic-review-and-meta-analysis
#18
Ying Wang, Min Ding, Qian Zhang, Jinghan Wang, Xijing Yang, Fuping Zhou, Linfang Li, Zhengang Yuan, Huajun Jin, Qijun Qian
Background: Infiltration of immune cells and immune microenvironment determine the proliferative activity of the tumor and metastasis. The aim of this study was to analyze the influence of activation or suppression of the immune response mediators on the prognosis of biliary tract cancer (BTC). Methods: We searched Pubmed, Web of Science, Embase and The Cochrane Library for relevant literatures until June 2016. The quality of studies was assessed by QUADAS-2 and NOS tools. Forest and funnel plots and all statistical analyses were generated by using Review Manager 5...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28109751/cord-blood-natural-killer-cells-expressing-a-dominant-negative-tgf-%C3%AE-receptor-implications-for-adoptive-immunotherapy-for-glioblastoma
#19
Eric S Yvon, Rachel Burga, Allison Powell, Conrad R Cruz, Rohan Fernandes, Cecilia Barese, Tuongvan Nguyen, Mohamed S Abdel-Baki, Catherine M Bollard
Cord blood (CB) natural killer (NK) cells are promising effector cells for tumor immunotherapy but are currently limited by immune-suppressive cytokines in the tumor microenvironment, such as transforming growth factor (TGF-β). We observed that TGF-β inhibits expression of activating receptors such as NKG2D and DNAM1 and decreases killing activity against glioblastoma tumor cells through inhibition of perforin secretion. To overcome the detrimental effects of TGF-β, we engrafted a dominant negative TGF-β receptor II (DNRII) on CB-derived NK cells by retroviral transduction and evaluated their ability to kill glioblastoma cells in the presence of TGF-β...
January 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28098874/mica-il-12-a-novel-bifunctional-protein-for-killer-cell-activation
#20
Ashlee Tietje, Xi Yang, Xianzhong Yu, Yanzhang Wei
Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors such as NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce the expression of these ligands, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, such as IL-12. A previous study in our laboratory showed that a fusion protein of the extracellular domain of mouse UL-16 binding protein-like transcript 1 (MULT1E) and mouse interleukin 12 (IL-12) can effectively activate mouse NK cells by in vitro assays and in vivo in animal tumor models...
January 16, 2017: Oncology Reports
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