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Nkg2d ligand

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https://www.readbyqxmd.com/read/29910819/decitabine-enhances-v%C3%AE-9v%C3%AE-2-t-cell-mediated-cytotoxic-effects-on-osteosarcoma-cells-via-the-nkg2dl-nkg2d-axis
#1
Zhan Wang, Zenan Wang, Shu Li, Binghao Li, Lingling Sun, Hengyuan Li, Peng Lin, Shengdong Wang, Wangsiyuan Teng, Xingzhi Zhou, Zhaoming Ye
γδ T cell-based immunotherapy for osteosarcoma (OS) has shown limited success thus far. DNA-demethylating agents not only induce tumor cell death but also have an immunomodulatory function. In this study, we have assessed the potential benefit of combining decitabine (DAC, a DNA demethylation drug) and γδ T cells for OS immunotherapy. DAC increased the expression of natural killer group 2D (NKG2D) ligands (NKG2DLs), including major histocompatibility complex class I-related chains B (MICB) and UL16-binding protein 1 (ULBP1), on the OS cell surface, making the cells more sensitive to recognition and destruction by cytotoxic γδ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910814/the-role-of-natural-killer-group-2-member-d-in-chronic-inflammation-and-autoimmunity
#2
REVIEW
Marina Babic, Chiara Romagnani
Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29892299/iq-domain-containing-gtpase-activating-protein-1-regulates-cytoskeletal-reorganization-and-facilitates-nkg2d-mediated-mechanistic-target-of-rapamycin-complex-1-activation-and-cytokine-gene-translation-in-natural-killer-cells
#3
Alex M Abel, Aradhana A Tiwari, Zachary J Gerbec, Jason R Siebert, Chao Yang, Nathan J Schloemer, Kate J Dixon, Monica S Thakar, Subramaniam Malarkannan
Natural killer (NK) cells are innate lymphocytes that play essential roles in mediating antitumor immunity. NK cells respond to various inflammatory stimuli including cytokines and stress-induced cellular ligands which activate germline-encoded activation receptors (NKRs), such as NKG2D. The signaling molecules activated downstream of NKRs are well defined; however, the mechanisms that regulate these pathways are not fully understood. IQ domain-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29868013/critical-contribution-of-nk-group-2-member-d-expressed-on-invariant-natural-killer-t-cells-in-concanavalin-a-induced-liver-hepatitis-in-mice
#4
Dina Al Dulaimi, Jihene Klibi, Veronica Olivo Pimentel, Veronique Parietti, Matthieu Allez, Antoine Toubert, Kamel Benlagha
Natural killer group 2D (NKG2D) is a well-characterized activating receptor expressed on many immune cells, including invariant natural killer T (iNKT) cells. These cells were shown to be responsible of liver injury in the model of concanavalin A (Con A)-induced hepatitis, considered to be an experimental model of human autoimmune hepatitis. In this study, we investigated whether NKG2D plays a role in the hepatitis induced by iNKT cell-mediated immune response to Con A. By using killer cell lectin-like receptor subfamily K, member 1 deficient ( Klrk1 -/- ) mice, we found that the absence of NKG2D reduced the hepatic injury upon Con A administration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867968/murine-cmv-expressing-the-high-affinity-nkg2d-ligand-mult-1-a-model-for-the-development-of-cytomegalovirus-based-vaccines
#5
Lea Hiršl, Ilija Brizić, Tina Jenuš, Vanda Juranić Lisnić, Johanna Julia Reichel, Slaven Jurković, Astrid Krmpotić, Stipan Jonjić
The development of a vaccine against human cytomegalovirus (CMV) has been a subject of long-term medical interest. The research during recent years identified CMV as an attractive vaccine vector against infectious diseases and tumors. The immune response to CMV persists over a lifetime and its unique feature is the inflationary T cell response to certain viral epitopes. CMV encodes numerous genes involved in immunoevasion, which are non-essential for virus growth in vitro . The deletion of those genes results in virus attenuation in vivo , which enables us to dramatically manipulate its virulence and the immune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867961/human-%C3%AE-%C3%AE-t-cells-from-surface-receptors-to-the-therapy-of-high-risk-leukemias
#6
REVIEW
Vito Pistoia, Nicola Tumino, Paola Vacca, Irene Veneziani, Alessandro Moretta, Franco Locatelli, Lorenzo Moretta
γδ T lymphocytes are potent effector cells, capable of efficiently killing tumor and leukemia cells. Their activation is mediated by γδ T-cell receptor (TCR) and by activating receptors shared with NK cells (e.g., NKG2D and DNAM-1). γδ T-cell triggering occurs upon interaction with specific ligands, including phosphoantigens (for Vγ9Vδ2 TCR), MICA-B and UL16 binding protein (for NKG2D), and PVR and Nectin-2 (for DNAM-1). They also respond to cytokines undergoing proliferation and release of cytokines/chemokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#7
Alessandra Zingoni, Elisabetta Vulpis, Francesca Cecere, Maria G Amendola, Daniel Fuerst, Taron Saribekyan, Adnane Achour, Tatyana Sandalova, Ilaria Nardone, Agnese Peri, Alessandra Soriani, Cinzia Fionda, Elena Mariggiò, Maria T Petrucci, Maria R Ricciardi, Joannis Mytilineos, Marco Cippitelli, Cristina Cerboni, Angela Santoni
Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29757143/tumor-derived-csf-1-induces-the-nkg2d-ligand-rae-1%C3%AE-on-tumor-infiltrating-macrophages
#8
Thornton W Thompson, Benjamin T Jackson, P Jonathan Li, Jiaxi Wang, Alexander Byungsuk Kim, Kristen Ting Hui Huang, Lily Zhang, David H Raulet
NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo ...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29750425/increased-infiltration-of-macrophages-to-radioresistant-lung-cancer-cells-contributes-to-the-development-of-the-additional-resistance-of-tumor-cells-to-the-cytotoxic-effects-of-nk-cells
#9
Mingjing Shen, Yongbing Chen, Lijun Xu, Rongying Zhu, Xiang Xue, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
In this study, in order to investigate the effects of increased macrophage infiltration to radioresistant lung tumors in regulating natural killer (NK) cell-mediated immunity, we examined whether the treatment of radioresistant cells with conditioned medium (CM) from phorbol myristate acetate (PMA)/interleukin (IL)-4 treated THP-1 cells (used as a tumor-associated macrophage source) leads to the development of the additional resistance of tumor cells to NK cell cytotoxicity. We found that the susceptibility of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity was decreased compared to the non-treated cells...
July 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29741244/enhanced-th1-and-inflammatory-mrna-responses-upregulate-nk-cell-cytotoxicity-and-nkg2d-ligand-expression-in-human-pre-eclamptic-placenta-and-target-it-for-nk-cell-attack
#10
Marie-Therese Vinnars, Emma Björk, Ivan Nagaev, Ulrika Ottander, Katarina Bremme, Ulrika Holmlund, Eva Sverremark-Ekström, Lucia Mincheva-Nilsson
PROBLEM: Pre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis...
May 9, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29740448/working-in-nk-mode-natural-killer-group-2-member-d-and-natural-cytotoxicity-receptors-in-stress-surveillance-by-%C3%AE-%C3%AE-t-cells
#11
REVIEW
Bruno Silva-Santos, Jessica Strid
Natural killer cell receptors (NKRs) are germline-encoded transmembrane proteins that regulate the activation and homeostasis of NK cells as well as other lymphocytes. For γδ T cells, NKRs play critical roles in discriminating stressed (transformed or infected) cells from their healthy counterparts, as proposed in the "lymphoid stress-surveillance" theory. Whereas the main physiologic role is seemingly fulfilled by natural killer group 2 member D, constitutively expressed by γδ T cells, enhancement of their therapeutic potential may rely on natural cytotoxicity receptors (NCRs), like NKp30 or NKp44, that can be induced selectively on human Vδ1+ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740438/the-nkg2d-nkg2dl-axis-in-the-crosstalk-between-lymphoid-and-myeloid-cells-in-health-and-disease
#12
REVIEW
Ana Stojanovic, Margareta P Correia, Adelheid Cerwenka
Natural killer group 2, member D (NKG2D) receptor is a type II transmembrane protein expressed by both innate and adaptive immune cells, including natural killer (NK) cells, CD8+ T cells, invariant NKT cells, γδ T cells, and some CD4+ T cells under certain pathological conditions. NKG2D is an activating NK receptor that induces cytotoxicity and production of cytokines by effector cells and supports their proliferation and survival upon engagement with its ligands. In both innate and T cell populations, NKG2D can costimulate responses induced by other receptors, such as TCR in T cells or NKp46 in NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29737430/hil-15-gene-modified-human-natural-killer-cells-nkl-il15-exhibit-anti-human-leukemia-functions
#13
Wen Jiang, Cai Zhang, Zhigang Tian, Jian Zhang
PURPOSE: Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo...
May 8, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29720199/immunoassays-for-scarce-tumour-antigens-in-exosomes-detection-of-the-human-nkg2d-ligand-mica-in-tetraspanin-containing-nanovesicles-from-melanoma
#14
Sheila López-Cobo, Carmen Campos-Silva, Amanda Moyano, Myriam Oliveira-Rodríguez, Annette Paschen, María Yáñez-Mó, María Carmen Blanco-López, Mar Valés-Gómez
BACKGROUND: Tumour-derived exosomes can be released to serum and provide information on the features of the malignancy, however, in order to perform systematic studies in biological samples, faster diagnostic techniques are needed, especially for detection of low abundance proteins. Most human cancer cells are positive for at least one ligand for the activating immune receptor NKG2D and the presence in plasma of NKG2D-ligands can be associated with prognosis. METHODS: Using MICA as example of a tumour-derived antigen, endogenously expressed in metastatic melanoma and recruited to exosomes, we have developed two immunocapture-based assays for detection of different epitopes in nanovesicles...
May 2, 2018: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29693186/combined-inhibition-of-jak1-2-stat3%C3%A2-pd%C3%A2-l1-signaling-pathway-suppresses-the-immune-escape-of-castration%C3%A2-resistant-prostate-cancer-to-nk-cells-in-hypoxia
#15
Li-Jun Xu, Qi Ma, Jin Zhu, Jian Li, Bo-Xin Xue, Jie Gao, Chuan-Yang Sun, Ya-Chen Zang, Yi-Bin Zhou, Dong-Rong Yang, Yu-Xi Shan
Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B (MICA/MICB) decreased...
June 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29690909/targeting-chemotherapy-resistant-leukemia-by-combining-dnt-cellular-therapy-with-conventional-chemotherapy
#16
Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D Minden, Li Zhang
BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy...
April 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29683892/implication-of-highly-cytotoxic-natural-killer-cells-for-esophageal-squamous-cell-carcinoma-treatment
#17
Kee Siang Lim, Kosaku Mimura, Ley-Fang Kua, Kensuke Shiraishi, Koji Kono
Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...
July 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29679656/pd-1-blocks-lytic-granule-polarization-with-concomitant-impairment-of-integrin-outside-in-signaling-in-the-natural-killer-cell-immunological-synapse
#18
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine the effect of PD-1 signaling on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29662484/nkg2d-and-its-ligands-one-for-all-all-for-one
#19
REVIEW
Alessandra Zingoni, Rosa Molfetta, Cinzia Fionda, Alessandra Soriani, Rossella Paolini, Marco Cippitelli, Cristina Cerboni, Angela Santoni
The activating receptor NKG2D is peculiar in its capability to bind to numerous and highly diversified MHC class I-like self-molecules. These ligands are poorly expressed on normal cells but can be induced on damaged, transformed or infected cells, with the final NKG2D ligand expression resulting from multiple levels of regulation. Although redundant molecular mechanisms can converge in the regulation of all NKG2D ligands, different stimuli can induce specific cellular responses, leading to the expression of one or few ligands...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29651291/cutting-an-nkg2d-ligand-short-cellular-processing-of-the-peculiar-human-nkg2d-ligand-ulbp4
#20
Tobias Zöller, Mareike Wittenbrink, Meike Hoffmeister, Alexander Steinle
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous "self cells" by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1-6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D-NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions...
2018: Frontiers in Immunology
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