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DNAM-1

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https://www.readbyqxmd.com/read/29202043/epstein-barr-virus-induces-adhesion-receptor-cd226-dnam-1-expression-during-primary-b-cell-transformation-into-lymphoblastoid-cell-lines
#1
Lisa Grossman, Chris Chang, Joanne Dai, Pavel A Nikitin, Dereje D Jima, Sandeep S Dave, Micah A Luftig
Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29182664/differential-inhibitory-and-activating-nk-cell-receptor-levels-and-nk-nkt-like-cell-functionality-in-chronic-and-recovered-stages-of-chikungunya
#2
Subrat Thanapati, Mohini A Ganu, Anuradha S Tripathy
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#3
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rgnull-mice
#4
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34+ hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29074605/allogeneic-human-double-negative-t-cells-as-a-novel-immunotherapy-for-acute-myeloid-leukemia-and-its-underlying-mechanisms
#5
Jong Bok Lee, Mark D Minden, Weihsu C Chen, Elena Streck, Branson Chen, Hyeonjeong Kang, Andrea Arruda, Dalam Ly, Sandy D Der, Sohyeong Kang, Paulina Achita, Cheryl D'Souza, Yueyang Li, Richard W Childs, John E Dick, Li Zhang
PURPOSE: To explore the potential of ex vivo expanded healthy donor derived allogeneic CD4 and CD8 double negative cells (DNTs) as a novel cellular immunotherapy for leukemia patients. EXPERIMENTAL DESIGN: Clinical grade DNTs from peripheral blood of healthy donors were expanded and their anti-leukemic activity and safety were examined using flow-cytometry based in vitro killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29061445/amelioration-of-nk-cell-function-driven-by-v%C3%AE-24-invariant-nkt-cell-activation-in-multiple-myeloma
#6
Tomonori Iyoda, Satoru Yamasaki, Michihiro Hidaka, Fumio Kawano, Yu Abe, Kenshi Suzuki, Norimitsu Kadowaki, Kanako Shimizu, Shin-Ichiro Fujii
NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells...
October 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28765218/dengue-virus-infected-dendritic-cells-but-not-monocytes-activate-natural-killer-cells-through-a-contact-dependent-mechanism-involving-adhesion-molecules
#7
Vivian Vasconcelos Costa, Weijian Ye, Qingfeng Chen, Mauro Martins Teixeira, Peter Preiser, Eng Eong Ooi, Jianzhu Chen
Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ...
August 1, 2017: MBio
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
#8
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/28561023/expression-of-cd226-is-associated-to-but-not-required-for-nk-cell-education
#9
Arnika K Wagner, Nadir Kadri, Johanna Snäll, Petter Brodin, Susan Gilfillan, Marco Colonna, Günter Bernhardt, Petter Höglund, Klas Kärre, Benedict J Chambers
DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28498033/development-and-characterization-of-novel-monoclonal-antibodies-against-human-dnam-1
#10
Genki Okumura, Fumie Abe, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human...
June 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28456791/nk-cells-and-multiple-myeloma-associated-endothelial-cells-molecular-interactions-and-influence-of-il-27
#11
Alessandra Dondero, Beatrice Casu, Francesca Bellora, Angelo Vacca, Annunziata De Luisi, Maria Antonia Frassanito, Claudia Cantoni, Silvia Gaggero, Daniel Olive, Alessandro Moretta, Cristina Bottino, Roberta Castriconi
Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#12
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28337208/natural-killer-cell-development-and-maturation-revisited-possible-implications-of-a-novel-distinct-lin-cd34-dnam-1-bright-cxcr4-cell-progenitor
#13
Federica Bozzano, Francesco Marras, Andrea De Maria
Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34(+) progenitors, in vivo and in vitro; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#14
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/28035916/the-paired-receptors-tigit-and-dnam-1-as-targets-for-therapeutic-antibodies
#15
Natan Stein, Pinchas Tsukerman, Ofer Mandelboim
One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling...
2017: Human Antibodies
https://www.readbyqxmd.com/read/27992381/low-dose-bortezomib-increases-the-expression-of-nkg2d-and-dnam-1-ligands-and-enhances-induced-nk-and-%C3%AE-%C3%AE-t-cell-mediated-lysis-in-multiple-myeloma
#16
Chao Niu, Haofan Jin, Min Li, Shan Zhu, Lei Zhou, Feng Jin, Yulai Zhou, Dongsheng Xu, Jianting Xu, Lianjing Zhao, Shanshan Hao, Wei Li, Jiuwei Cui
Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) or γδ T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and γδ T cells further improves outcomes in MM, and how the treatments should be combined, remain unclear. Herein, we found that low-dose bortezomib did not suppress the viability of induced NK and γδ T cells, but did induce MM cell apoptosis...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27919749/in-vitro-vla-4-blockade-results-in-an-impaired-nk-cell-mediated-immune-surveillance-against-melanoma
#17
Ilaria Gandoglia, Federico Ivaldi, Paolo Carrega, Eric Armentani, Guido Ferlazzo, Gianluigi Mancardi, Nicole Kerlero de Rosbo, Antonio Uccelli, Alice Laroni
Natalizumab (NTZ) is a monoclonal antibody targeting the α4β1 integrin (CD49d/CD29), very late antigen-4 (VLA-4), which is approved for treatment of relapsing-remitting multiple sclerosis (RR-MS). A possible association between NTZ treatment and a higher risk of melanoma is under debate. Natural Killer (NK) cells, which express VLA-4, represent an innate barrier limiting spreading of melanoma under steady state conditions. Indeed, because of their expression of activating receptors, they are very efficient in recognizing and killing melanoma cells without the need of a previous priming...
December 2, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27884732/natural-killer-cell-subsets-and-receptor-expression-in-peripheral-blood-mononuclear-cells-of-a-healthy-korean-population-reference-range-influence-of-age-and-sex-and-correlation-between-nk-cell-receptors-and-cytotoxicity
#18
Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, Duck Cho
BACKGROUND: The purpose of this study was to identify CD56(bright) and CD56(dim) natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3(-)/CD56(dim) and CD3(-)/CD56(bright) NK cells in whole-blood samples from 122 healthy donors...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#19
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27783105/high-efficiency-lysis-of-cervical-cancer-by-allogeneic-nk-cells-derived-from-umbilical-cord-progenitors-is-independent-of-hla-status
#20
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
January 2017: Cancer Immunology, Immunotherapy: CII
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