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Nkg2d ligand

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https://www.readbyqxmd.com/read/28087665/nkg2d-promotes-b1a-cell-development-and-protection-against-bacterial-infection
#1
Maja Lenartić, Vedrana Jelenčić, Biljana Zafirova, Mateja Ožanič, Valentina Marečić, Slaven Jurković, Veronika Sexl, Marina Šantić, Felix M Wensveen, Bojan Polić
NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28055304/synergistic-effect-of-cytokine-induced-killer-cell-with-valproate-inhibits-growth-of-hepatocellular-carcinoma-cell-in-a-mouse-model
#2
Dong Hyeon Lee, Joon Yeul Nam, Young Chang, Hyeki Cho, Seong Hee Kang, Young Youn Cho, EunJu Cho, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
OBJECTIVE: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC...
January 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28031333/t-cells-infiltrating-diseased-liver-express-ligands-for-the-nkg2d-stress-surveillance-system
#3
Wei-Chen Huang, Nicholas J Easom, Xin-Zi Tang, Upkar S Gill, Harsimran Singh, Francis Robertson, Chiwen Chang, John Trowsdale, Brian R Davidson, William M Rosenberg, Giuseppe Fusai, Antoine Toubert, Patrick T Kennedy, Dimitra Peppa, Mala K Maini
NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)-specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28018354/impact-of-the-mica-129met-val-dimorphism-on-nkg2d-mediated-biological-functions-and-disease-risks
#4
REVIEW
Antje Isernhagen, Dörthe Malzahn, Heike Bickeböller, Ralf Dressel
The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8(+) T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val)...
2016: Frontiers in Immunology
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
#5
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...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27956531/clr-a-a-novel-immune-related-c-type-lectin-like-molecule-exclusively-expressed-by-mouse-gut-epithelium
#6
Emilia Rutkowski, Stefan Leibelt, Christina Born, Miriam E Friede, Stefan Bauer, Sandra Weil, Joachim Koch, Alexander Steinle
The mouse gut epithelium represents a constitutively challenged environment keeping intestinal commensal microbiota at bay and defending against invading enteric pathogens. The complex immunoregulatory network of the epithelial barrier surveillance also involves NK gene complex (NKC)-encoded C-type lectin-like molecules such as NKG2D and Nkrp1 receptors. To our knowledge, in this study, we report the first characterization of the orphan C-type lectin-like molecule Clr-a encoded by the Clec2e gene in the mouse NKC...
December 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#7
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
#8
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
#9
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
#10
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...
January 3, 2017: 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
#11
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...
January 2017: IUBMB Life
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#12
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
#13
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
#14
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...
December 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27833611/activated-allogeneic-nk-cells-preferentially-kill-poor-prognosis-b-cell-chronic-lymphocytic-leukemia-cells
#15
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
#16
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
#17
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
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (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...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27783394/association-of-nkg2d-gene-variants-with-susceptibility-and-severity-of-rheumatoid-arthritis
#18
C M Mariaselvam, R Tamouza, R Krishnamoorthy, D Charron, D P Misra, V K Jain, V S Negi
NKG2D (KLRK1) is a C-type lectin receptor present on natural killer (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
#19
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
#20
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
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