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https://www.readbyqxmd.com/read/28811958/soluble-nkg2d-ligands-are-biomarkers-associated-with-the-clinical-outcome-to-immune-checkpoint-blockade-therapy-of-metastatic-melanoma-patients
#1
Cristina Maccalli, Diana Giannarelli, Carla Chiarucci, Ornella Cutaia, Gianluca Giacobini, Wouter Hendrickx, Giovanni Amato, Diego Annesi, Davide Bedognetti, Maresa Altomonte, Riccardo Danielli, Luana Calabrò, Anna Maria Di Giacomo, Francesco M Marincola, Giorgio Parmiani, Michele Maio
The introduction of immune checkpoint blockade into the clinical practice resulted in improvement of survival of a significant portion of melanoma patients. Consequently, predictive biomarkers of response are needed to optimize patient's stratification and the development of combination therapies. The aim of this study was to determine whether levels of soluble NKG2D ligands (MICA, MICB, ULBP1, 2 and 3; sNKG2DLs) in the serum of melanoma patients can serve as useful predictors of response to the treatment with immune checkpoint blockade...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28747426/intestinal-epithelial-cell-endoplasmic-reticulum-stress-promotes-mult1-up-regulation-and-nkg2d-mediated-inflammation
#2
Shuhei Hosomi, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D Matute, Magdalena B Flak, Eduardo Martinez-Naves, Manuel Gomez Del Moral, Jonathan N Glickman, Mizuki Ohira, Lewis L Lanier, Arthur Kaser, Richard Blumberg
Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1(ΔIEC) ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28689087/the-histone-deacetylase-inhibitor-saha-simultaneously-reactivates-hiv-1-from-latency-and-up-regulates-nkg2d-ligands-sensitizing-for-natural-killer-cell-cytotoxicity
#3
Maria Giovanna Desimio, Erica Giuliani, Margherita Doria
In pilot HIV-1 eradication studies, patients' immune responses were ineffective at killing viral reservoirs reactivated through latency reversing agents (LRAs) like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using latently HIV-1-infected J-Lat 6.3/8.4/9...
July 6, 2017: Virology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#4
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#5
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/28559451/a-disease-linked-ulbp6-polymorphism-inhibits-nkg2d-mediated-target-cell-killing-by-enhancing-the-stability-of-nkg2d-ligand-binding
#6
Jianmin Zuo, Carrie R Willcox, Fiyaz Mohammed, Martin Davey, Stuart Hunter, Kabir Khan, Ayman Antoun, Poonam Katakia, Joanne Croudace, Charlotte Inman, Helen Parry, David Briggs, Ram Malladi, Benjamin E Willcox, Paul Moss
NKG2D (natural killer group 2, member D) is an activating receptor found on the surface of immune cells, including natural killer (NK) cells, which regulates innate and adaptive immunity through recognition of the stress-induced ligands ULBP1 (UL16 binding protein 1) to ULBP6 and MICA/B. Similar to class I human leukocyte antigen (HLA), these NKG2D ligands have a major histocompatibility complex-like fold and exhibit pronounced polymorphism, which influences human disease susceptibility. However, whereas class I HLA polymorphisms occur predominantly in the α1α2 groove and affect antigen binding, the effects of most NKG2D ligand polymorphisms are unclear...
May 30, 2017: Science Signaling
https://www.readbyqxmd.com/read/28433635/prognostic-significance-and-functional-implication-of-immune-activating-receptor-nkg2d-in-gastric-cancer
#7
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...
June 3, 2017: Biochemical and Biophysical Research Communications
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
#8
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/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#9
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/28165192/the-tgf-%C3%AE-induced-up-regulation-of-nkg2dls-requires-akt-gsk-3%C3%AE-mediated-stabilization-of-sp1
#10
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...
May 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27874833/a-herpesviral-induction-of-rae-1-nkg2d-ligand-expression-occurs-through-release-of-hdac-mediated-repression
#11
Trever T Greene, Maria Tokuyama, Giselle M Knudsen, Michele Kunz, James Lin, Alexander L Greninger, Victor R DeFilippis, Joseph L DeRisi, David H Raulet, Laurent Coscoy
Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands...
November 22, 2016: ELife
https://www.readbyqxmd.com/read/27733551/distinct-roles-for-human-cytomegalovirus-immediate-early-proteins-ie1-and-ie2-in-the-transcriptional-regulation-of-mica-and-pvr-cd155-expression
#12
Benedetta Pignoloni, Cinzia Fionda, Valentina Dell'Oste, Anna Luganini, Marco Cippitelli, Alessandra Zingoni, Santo Landolfo, Giorgio Gribaudo, Angela Santoni, Cristina Cerboni
Elimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I-related chain (MIC) A/B and UL16-binding proteins (ULBP)1-6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell-mediated lysis of infected cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27633889/harnessing-bioinformatics-for-designing-a-novel-multiepitope-peptide-vaccine-against-breast-cancer
#13
Shirin Mahmoodi, Navid Nezafat, Abolfazl Barzegar, Manica Negahdaripour, Ali R Nikanfar, Nosratollah Zarghami, Younes Ghasemi
Breast cancer (BC) remains as one of the important causes of cancer deaths among women globally. Therefore, finding an effective treatment for BC is really needed. Cancer immunotherapy, as an emerging field, has a notable role in BC therapy. Peptide vaccines possess an outstanding role among different strategies in cancer immunotherapy. In vaccine design for cancer, induction of cellular and humoral immune responses should be considered. In the current study, cytolytic T lymphocytes (CTL) epitopes were evoked from human epidermal growth factor receptor (HER2), mucin 1 protein (MUC1), and heparanase antigenic proteins; and helper T lymphocytes (HTL) epitopes were determined from survivin protein by various immunoinformatics servers...
2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27621649/expression-and-prognostic-significance-of-unique-ulbps-in-pancreatic-cancer
#14
Jiong Chen, Xing-Xing Zhu, Hong Xu, Heng-Zhong Fang, Jin-Qian Zhao
BACKGROUND: Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27580123/natural-killer-cell-evasion-is-essential-for-infection-by-rhesus-cytomegalovirus
#15
Elizabeth R Sturgill, Daniel Malouli, Scott G Hansen, Benjamin J Burwitz, Seongkyung Seo, Christine L Schneider, Jennie L Womack, Marieke C Verweij, Abigail B Ventura, Amruta Bhusari, Krystal M Jeffries, Alfred W Legasse, Michael K Axthelm, Amy W Hudson, Jonah B Sacha, Louis J Picker, Klaus Früh
The natural killer cell receptor NKG2D activates NK cells by engaging one of several ligands (NKG2DLs) belonging to either the MIC or ULBP families. Human cytomegalovirus (HCMV) UL16 and UL142 counteract this activation by retaining NKG2DLs and US18 and US20 act via lysomal degradation but the importance of NK cell evasion for infection is unknown. Since NKG2DLs are highly conserved in rhesus macaques, we characterized how NKG2DL interception by rhesus cytomegalovirus (RhCMV) impacts infection in vivo. Interestingly, RhCMV lacks homologs of UL16 and UL142 but instead employs Rh159, the homolog of UL148, to prevent NKG2DL surface expression...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27183434/the-effect-of-g2-adjuvant-on-gene-expression-and-delivery-of-nkg2d-receptor-on-nk-cells-in-peripheral-blood
#16
Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian Boroujerdnia, Mohammad-Ali Assarehzadegan, Mohammad Ghasemi, Saleh Mohaghegh Hazrati, Nader Dashti Gerdabi
INTRODUCTION: Natural killer (NK) cells are a subset of lymphocytes in humans that release cytokines such as tumor necrosis factor alpha and interferon gamma-γ during infection. NKG2D is one of the most important stimulating NK receptors binding MIC-A, MIC-B, and ULBPs, which leads to activation of NK cells against tumor cells. In this study, the authors evaluated the effect of G2 adjuvant on gene expression and delivery of NKG2D receptor on NK cells in peripheral blood. MATERIALS AND METHODS: Peripheral blood mononuclear cells were isolated from venous blood obtained from healthy volunteers after adding G2 adjuvant within 12, 24, and 48 hours of incubation...
May 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27166406/variations-in-patterns-of-utilization-and-charges-for-the-care-of-low-back-pain-in-north-carolina-2000-to-2009-a-statewide-claims-data-analysis
#17
Eric L Hurwitz, Dongmei Li, Jenni Guillen, Michael J Schneider, Joel M Stevans, Reed B Phillips, Shawn P Phelan, Eugene A Lewis, Richard C Armstrong, Maria Vassilaki
OBJECTIVES: The purpose of the study was to compare utilization and charges generated by medical doctors (MD), doctors of chiropractic (DC) and physical therapists (PT) by patterns of care for the treatment of low back pain in North Carolina. METHODS: This was an analysis of low-back-pain-related closed claim data from the North Carolina State Health Plan for Teachers and State Employees from 2000 to 2009. Data were extracted from Blue Cross Blue Shield of North Carolina for the North Carolina State Health Plan using International Classification of Diseases, 9th Revision diagnostic codes for uncomplicated low back pain (ULBP) and complicated low back pain (CLBP)...
May 2016: Journal of Manipulative and Physiological Therapeutics
https://www.readbyqxmd.com/read/27158340/epirubicin-pretreatment-enhances-nk-cell-mediated-cytotoxicity-against-breast-cancer-cells-in-vitro
#18
Hui Feng, Ying Dong, Jing Wu, Yuan Qiao, Ge Zhu, Haofan Jin, Jiuwei Cui, Wei Li, Yong-Jun Liu, Jingtao Chen, Yanqiu Song
Anthracycline-based chemotherapy is a conventional treatment for breast cancer. However, it can negatively affect host immune function and thereby impair patients' quality of life. Boosting the host immune system and reducing the adverse effect of chemotherapy are important for effective cancer treatment. Natural killer (NK) cells stimulate immune responses against cancer; autologous immune enhancement therapy with NK cells prolongs patient survival without significant adverse effects. This study investigated the effects of combined treatment with the anthracycline agent epirubicin (EPI) and NK cells on human breast cancer cells...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27141379/overexpression-of-kir-inhibitory-ligands-hla-i-determines-that-immunosurveillance-of-myeloma-depends-on-diverse-and-strong-nk-cell-licensing
#19
María V Martínez-Sánchez, Adela Periago, Isabel Legaz, Lourdes Gimeno, Anna Mrowiec, Natividad R Montes-Barqueros, José A Campillo, José M Bolarin, María V Bernardo, María R López-Álvarez, Consuelo González, María C García-Garay, Manuel Muro, Valentin Cabañas-Perianes, Jose L Fuster, Ana M García-Alonso, José M Moraleda, María R Álvarez-Lopez, Alfredo Minguela
Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1(-)L2(+)L3(-) genotypes (2...
April 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27141377/nkg2d-and-t-cell-receptor-dependent-lysis-of-malignant-glioma-cell-lines-by-human-%C3%AE-%C3%AE-t-cells-modulation-by-temozolomide-and-a-disintegrin-and-metalloproteases-10-and-17-inhibitors
#20
Guranda Chitadze, Marcus Lettau, Stefanie Luecke, Ting Wang, Ottmar Janssen, Daniel Fürst, Joannis Mytilineos, Daniela Wesch, Hans-Heinrich Oberg, Janka Held-Feindt, Dieter Kabelitz
The interaction of the MHC class I-related chain molecules A and B (MICA and MICB) and UL-16 binding protein (ULBP) family members expressed on tumor cells with the corresponding NKG2D receptor triggers cytotoxic effector functions in NK cells and γδ T cells. However, as a mechanism of tumor immune escape, NKG2D ligands (NKG2DLs) can be released from the cell surface. In this study, we investigated the NKG2DL system in different human glioblastoma (GBM) cell lines, the most lethal brain tumor in adults. Flow cytometric analysis and ELISA revealed that despite the expression of various NKG2DLs only ULBP2 is released as a soluble protein via the proteolytic activity of "a disintegrin and metalloproteases" (ADAM) 10 and 17...
April 2016: Oncoimmunology
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