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Nkg2d ligand

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https://www.readbyqxmd.com/read/29422899/sensing-bacterial-induced-dna-damaging-effects-via-natural-killer-group-2-member-d-immune-receptor-from-dysbiosis-to-autoimmunity-and-carcinogenesis
#1
REVIEW
J Luis Espinoza, Mika Minami
The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29408565/in-vitro-induced-m2-type-macrophages-induces-the-resistance-of-prostate-cancer-cells-to-cytotoxic-action-of-nk-cells
#2
Lijun Xu, Mingjing Shen, Xiaodong Chen, Dong-Rong Yang, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells...
January 31, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29400704/functions-of-nkg2d-in-cd8-t-cells-an-opportunity-for-immunotherapy
#3
REVIEW
Kushal Prajapati, Cynthia Perez, Lourdes Beatriz Plaza Rojas, Brianna Burke, Jose A Guevara-Patino
Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8+ T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8+ T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling...
February 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29356965/nkg2d-ligands-in-glioma-stem-like-cells-expression-in-situ-and-in-vitro
#4
Charlotte Flüh, Guranda Chitadze, Vivian Adamski, Kirsten Hattermann, Michael Synowitz, Dieter Kabelitz, Janka Held-Feindt
Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Tumor stem cells have a major influence on tumor malignancy, and immunological escape mechanisms, involving the Natural Killer Group 2, member D (NKG2D) receptor-ligand-system, are key elements in tumor immuno-surveillance. We analyzed the expression profile and localization of NKG2D ligands (NKG2DL) and embryonic and neural stem cell markers in solid human GBM and stem-like cells isolated from glioma cell lines by qRT-PCR and immunohistochemistry, including quantitative analysis...
January 22, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#5
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29316666/fusion-proteins-of-nkg2d-nkg2dl-in-cancer-immunotherapy
#6
REVIEW
Hui Ding, Xi Yang, Yanzhang Wei
NKG2D (natural killer group 2, member D) is an important activating receptor in natural killer (NK) cells and some T cells. NKG2D ligands (NKG2DLs) are specifically expressed on most tumor cells. The engagement of these ligands on tumor cells to NKG2D on NK cells will induce cell-mediated cytotoxicity and have target cells destroyed. This gives NKG2D/NKG2DLs great potential in cancer therapeutic application. The creation of NKG2D/NKG2DL-based multi-functional fusion proteins is becoming one of the most promising strategies in immunotherapy for cancer...
January 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29279329/purine-nucleotide-metabolism-regulates-expression-of-the-human-immune-ligand-mica
#7
Michael T McCarthy, Gerald Moncayo, Thomas K Hiron, Niels A Jakobsen, Alessandro Vali, Tomoyoshi Soga, Julie Adam, Christopher A O'Callaghan
Expression of the cell surface glycoprotein MHC class I polypeptide-related sequence A (MICA) is induced in dangerous, abnormal or 'stressed' cells, including cancer cells, virus-infected cells and rapidly proliferating cells. MICA is recognized by the activating immune cell receptor NKG2D, providing a mechanism by which immune cells can identify and potentially eliminate pathological cells. Immune recognition through NKG2D is implicated in cancer, atherosclerosis, transplant rejection and inflammatory diseases such as rheumatoid arthritis...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29231815/endothelial-cells-express-nkg2d-ligands-and-desensitize-anti-tumor-nk-responses
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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