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Nkg2d ligand

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https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#1
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#2
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27874833/a-herpesviral-induction-of-rae-1-nkg2d-ligand-expression-occurs-through-release-of-hdac-mediated-repression
#3
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/27869649/randomized-trial-of-calcipotriol-combined-with-5-fluorouracil-for-skin-cancer-precursor-immunotherapy
#4
Trevor J Cunningham, Mary Tabacchi, Jean-Pierre Eliane, Sara Moradi Tuchayi, Sindhu Manivasagam, Hengameh Mirzaalian, Ahu Turkoz, Raphael Kopan, Andras Schaffer, Arturo P Saavedra, Michael Wallendorf, Lynn A Cornelius, Shadmehr Demehri
BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27868339/fasl-and-the-nkg2d-receptor-are-required-for-the-secretion-of-the-tag7-pgrp-s-hsp70-complex-by-the-cytotoxic-cd8-lymphocytes
#5
Lidia P Sashchenko, Elena A Romanova, Olga K Ivanova, Tatiana N Sharapova, Denis V Yashin
Tag7 (PGRP-S or PGLYRP1), while possessing an antimicrobial activity, also exhibits an antitumor effect when in complex with the major heat shock protein Hsp70. The cytotoxic Tag7-Hsp70 complex is secreted by lymphocytes after interaction with the HLA-negative tumors. Previously, we have shown that IL-2 induces formation of the CD4(+) and CD8(+) cytotoxic subpopulations of human lymphocytes, which kill tumor cells through the FasL-Fas interaction. Here, we show that only the CD8(+) T cells are able to secrete the Tag7-Hsp70 complex...
November 20, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#6
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/27849169/mechanisms-of-acute-toxicity-in-nkg2d-chimeric-antigen-receptor-t-cell-treated-mice
#7
Marie-Louise Sentman, Joana M Murad, W James Cook, Ming-Ru Wu, Jake Reder, Susanne H Baumeister, Glenn Dranoff, Michael W Fanger, Charles L Sentman
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27834580/nkg2d-ligand-expression-in-pediatric-brain-tumors
#8
Kristen Haberthur, Kathryn Brennan, Virginia Hoglund, Stephanie Balcaitis, Harrison Chinn, Amira Davis, Shannon Kreuser, Conrad Winter, Sarah E S Leary, Gail H Deutsch, Richard G Ellenbogen, Courtney A Crane
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells...
November 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27833611/activated-allogeneic-nk-cells-preferentially-kill-poor-prognosis-b-cell-chronic-lymphocytic-leukemia-cells
#9
Diego Sánchez-Martínez, Pilar M Lanuza, Natalia Gómez, Aura Muntasell, Elisa Cisneros, Manuela Moraru, Gemma Azaceta, Alberto Anel, Luis Martínez-Lostao, Martin Villalba, Luis Palomera, Carlos Vilches, José A García Marco, Julián Pardo
Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#10
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27811019/matching-for-the-mica-129-polymorphism-is-beneficial-in-unrelated-hematopoietic-stem-cell-transplantation
#11
Daniel Fuerst, Christine Neuchel, Dietger Niederwieser, Donald Bunjes, Martin Gramatzki, Eva Wagner, Gerald Wulf, Bertram Glass, Michael Pfreundschuh, Hermann Einsele, Renate Arnold, Gernot Stuhler, Kerstin Schaefer-Eckart, Sebastian Freitag, Jochen Casper, Martin Kaufmann, Mohammed Wattad, Bernd Hertenstein, Stefan Klein, Mark Ringhoffer, Daphne Mytilineos, Chrysanthi Tsamadou, Carlheinz Mueller, Hubert Schrezenmeier, Joannis Mytilineos
MICA (MHC class I polypeptide-related sequence A) is a highly polymorphic ligand of the activating NKG2D receptor on NK-cells, γδ-T-cells and NKT-cells. MICA incompatibilities have been associated with an increased GvHD incidence and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA-matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n=1379), 9/10 (n=636) or 8/10 (n=157) HLA-alleles...
November 3, 2016: Blood
https://www.readbyqxmd.com/read/27783394/association-of-nkg2d-gene-variants-with-susceptibility-and-severity-of-rheumatoid-arthritis
#12
Christina M Mariaselvam, Ryad Tamouza, Rajagopal Krishnamoorthy, Dominique Charron, Durga Prasanna Misra, Vikramraj K Jain, Vir Singh Negi
INTRODUCTION: NKG2D (KLRK1) is a C-type lectin receptor present on NK cells, γδ, CD8(+) and CD4(+) T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with Rheumatoid Arthritis (RA)...
October 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27757305/mono-and-dual-targeting-triplebodies-activate-natural-killer-cells-and-have-anti-tumor-activity-in-vitro-and-in-vivo-against-chronic-lymphocytic-leukemia
#13
Maulik Vyas, Ann-Charlott Schneider, Olga Shatnyeva, Katrin S Reiners, Samir Tawadros, Stephan Kloess, Ulrike Köhl, Michael Hallek, Hinrich P Hansen, Elke Pogge von Strandmann
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8(+) T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. Triplebodies in both formats showed better ability to induce NK-cell-dependent killing of target cells compared to bispecific counterparts...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27756784/tgf%C3%AE-r1-blockade-with-galunisertib-ly2157299-enhances-anti-neuroblastoma-activity-of-anti-gd2-antibody-dinutuximab-ch14-18-with-natural-killer-cells
#14
Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim, Shahab Asgharzadeh, Robert C Seeger
PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL DESIGN: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis...
October 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27734028/nk-cell-activating-receptor-ligand-expression-in-lymphangioleiomyomatosis-is-associated-with-lung-function-decline
#15
Andrew R Osterburg, Rebecca L Nelson, Benyamin Z Yaniv, Rachel Foot, Walter R F Donica, Madison A Nashu, Huan Liu, Kathryn A Wikenheiser-Brokamp, Joel Moss, Nishant Gupta, Francis X McCormack, Michael T Borchers
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules...
October 6, 2016: JCI Insight
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
#16
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...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27684826/in-vivo-expansion-and-activation-of-%C3%AE-%C3%AE-t-cells-as-immunotherapy-for-refractory-neuroblastoma-a-phase-1-study
#17
Joseph G Pressey, Julia Adams, Lualhati Harkins, David Kelly, Zhiying You, Lawrence S Lamb
INTRODUCTION: CD3+ γδ+ T cells comprise 2% to 5% of circulating T cells with Vγ9Vδ2+ cells the dominant circulating subtype. Vγ9Vδ2+ cells recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate the tumoricidal properties of γδ T cells represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB). In this prospective, non-randomized Phase I trial, we assessed whether circulating Vγ9Vδ2+ cells could be safely expanded using intravenous ZOL (Zoledronate [Zometa]) and subcutaneous Interleukin-2 (IL-2) in patients with refractory NB...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27672635/glycosyl-phosphatidyl-inositol-gpi-anchors-and-metalloproteases-their-roles-in-the-regulation-of-exosome-composition-and-nkg2d-mediated-immune-recognition
#18
REVIEW
Sheila López-Cobo, Carmen Campos-Silva, Mar Valés-Gómez
Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27671170/combination-treatment-with-decitabine-and-ionizing-radiation-enhances-tumor-cells-susceptibility-of-t-cells
#19
Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh, Dong-Yeok Shin, Jae-Ho Bae, Kwangmo Yang, You-Soo Park
Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27667711/regulation-of-nkg2d-expression-and-signaling-by-endocytosis
#20
Rosa Molfetta, Linda Quatrini, Beatrice Zitti, Cristina Capuano, Ricciarda Galandrini, Angela Santoni, Rossella Paolini
NKG2D is an activating receptor that can bind to a large number of stress-induced ligands that are expressed in the context of cancer or viral infection. This receptor is expressed on many cytotoxic lymphocytes, and plays a crucial role in antitumor and antiviral immune responses. However, exposure to NKG2D ligand-expressing target cells promotes receptor endocytosis, ultimately leading to lysosomal receptor degradation and impairment of NKG2D-mediated functions. Interestingly, before being degraded, internalized receptors can signal from the endosomal compartment, leading to the appropriate activation of cellular functional programs...
September 22, 2016: Trends in Immunology
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