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Nkg2d ligand

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https://www.readbyqxmd.com/read/29231815/endothelial-cells-express-nkg2d-ligands-and-desensitize-anti-tumor-nk-responses
#1
Thornton W Thompson, Alexander Byungsuk Kim, Po-Yi Jonathan Li, Jiaxi Wang, Benjamin T Jackson, Kristen Ting Hui Huang, Lily Zhang, David H Raulet
Natural Killer (NK) cells confer protection from tumors and infections by releasing cytotoxic granules and pro-inflammatory cytokines upon recognition of diseased cells. The responsiveness of NK cells to acute stimulation is dynamically tuned by steady-state receptor-ligand interactions of an NK cell with its cellular environment. Here we demonstrate that in healthy WT mice the NK activating receptor NKG2D is engaged in vivo by one of its ligands, RAE-1ε, which is expressed constitutively by lymph node endothelial cells and highly induced on tumor-associated endothelium...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29209320/how-mucosal-epithelia-deal-with-stress-role-of-nkg2d-nkg2d-ligands-during-inflammation
#2
REVIEW
Fabrizio Antonangeli, Alessandra Soriani, Cristina Cerboni, Giuseppe Sciumè, Angela Santoni
Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activating NKG2D receptor is one of the most direct mechanisms involved in the recognition of stressed cells by the immune system. Indeed, injured cells promptly express NKG2D ligands that in turn mediate the activation of lymphocytes of both innate and adaptive arms of the immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29190907/profile-of-differentially-expressed-toll-like-receptor-signaling-genes-in-the-natural-killer-cells-of-patients-with-s%C3%A3-zary-syndrome
#3
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29165229/na%C3%A3-ve-t-cells-are-activated-by-autologous-hcmv-infected-endothelial-cells-through-nkg2d-and-can-control-hcmv-transmission-in-vitro
#4
Narmadha Subramanian, Zeguang Wu, Frank Reister, Kerstin Laib Sampaio, Giada Frascaroli, Luka Cicin-Sain, Thomas Mertens
Apart from classical antigen-presenting cells (APCs) like dendritic cells and macrophages, there are semiprofessional APCs such as endothelial cells (ECs) and Langerhans' cells. Human cytomegalovirus (HCMV) infects a wide range of cell types including the ECs which are involved in the trafficking and homing of T cells. By investigating the interaction of naïve T cells obtained from HCMV-seronegative umbilical cord blood with autologous HCMV-infected human umbilical vein ECs (HUVECs), we could show that the activation of naïve T cells occurred after 1 day of peripheral blood mononuclear cell (PBMC) exposure to HCMV-infected HUVECs...
November 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29163533/chronic-nkg2d-engagement-in-vivo-differentially-impacts-nk-cell-responsiveness-by-activating-nk-receptors
#5
Christine Koch, Younghoon Kim, Tobias Zöller, Christina Born, Alexander Steinle
Immunosuppression is a typical hallmark of cancer and frequently includes perturbations of the NKG2D tumor recognition system as well as impaired signaling by other activating NK cell receptors. Several in vitro studies suggested that sustained engagement of the NKG2D receptor, as it is occurring in the tumor microenvironment, not only impairs expression and function of NKG2D but also impacts signaling by other activating NK receptors. Here, we made use of a transgenic mouse model of ubiquitous NKG2D ligand expression (H2-Kb-MICA mice) to investigate consequences of chronic NKG2D engagement in vivo for functional responsiveness by other activating NK receptors such as NKp46 and Ly49D...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#6
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#7
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rgnull-mice
#8
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/29133316/study-protocol-for-think-a-multinational-open-label-phase-i-study-to-assess-the-safety-and-clinical-activity-of-multiple-administrations-of-nkr-2-in-patients-with-different-metastatic-tumour-types
#9
Caroline Lonez, Bikash Verma, Alain Hendlisz, Philippe Aftimos, Ahmad Awada, Eric Van Den Neste, Gaetan Catala, Jean-Pascal H Machiels, Fanny Piette, Jason B Brayer, David A Sallman, Tessa Kerre, Kunle Odunsi, Marco L Davila, David E Gilham, Frédéric F Lehmann
INTRODUCTION: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29123961/soluble-nkg2d-ligands-limit-the-efficacy-of-immune-checkpoint-blockade
#10
EDITORIAL
Alejandro López-Soto, Segundo Gonzalez, Lorenzo Galluzzi
No abstract text is available yet for this article.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29113321/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#11
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29074605/allogeneic-human-double-negative-t-cells-as-a-novel-immunotherapy-for-acute-myeloid-leukemia-and-its-underlying-mechanisms
#12
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
#13
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/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#14
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28986447/innate-immune-recognition-of-double-stranded-rna-triggers-increased-expression-of-nkg2d-ligands-after-virus-infection
#15
Gloria Esteso, Susana Guerra, Mar Valés-Gómez, Hugh T Reyburn
Self/non-self discrimination by the innate immune system relies on germline-encoded, non-rearranging receptors expressed by innate immune cells recognizing conserved pathogen-associated molecular patterns. The natural killer group 2D (NKG2D) receptor is a potent immune-activating receptor that binds human genome-encoded ligands, whose expression is negligible in normal tissues, but increased in stress and disease conditions for reasons that are incompletely understood. Here it is not clear how the immune system reconciles receptor binding of self-proteins with self/non-self discrimination to avoid autoreactivity...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28944101/soluble-micb-in-plasma-and-urine-explains-population-expansions-of-nkg2d-cd4-t-cells-inpatients-with-juvenile-onset-systemic-lupus-erythematosus
#16
Satoru Hamada, Andrea Caballero-Benitez, Kate L Duran, Anne M Stevens, Thomas Spies, Veronika Groh
Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study's goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D(+)CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D(+)CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes...
March 2017: Open Journal of Immunology
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#17
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#18
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#19
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28926962/anti-nkg2d-mab-a-new-treatment-for-crohn-s-disease
#20
REVIEW
Kasper Vadstrup, Flemming Bendtsen
Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells...
September 16, 2017: International Journal of Molecular Sciences
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