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https://www.readbyqxmd.com/read/28708284/cd20-specific-immunoligands-engaging-nkg2d-enhance-%C3%AE-%C3%AE-t-cell-mediated-lysis-of-lymphoma-cells
#1
Matthias Peipp, Daniela Wesch, Hans-Heinrich Oberg, Sebastian Lutz, Anja Muskulus, Jan G J van de Winkel, Paul W H I Parren, Renate Burger, Andreas Humpe, Dieter Kabelitz, Martin Gramatzki, Christian Kellner
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumor cell killing...
July 14, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28701757/oncolytic-measles-virus-enhances-antitumour-responses-of-adoptive-cd8-nkg2d-cells-in-hepatocellular-carcinoma-treatment
#2
Aiping Chen, Yonghui Zhang, Gang Meng, Dengxu Jiang, Hailin Zhang, Meihong Zheng, Mao Xia, Aiqin Jiang, Junhua Wu, Christian Beltinger, Jiwu Wei
There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8(+)NKG2D(+) cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8(+)NKG2D(+) cells, mediated by at least three distinct mechanisms...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693159/cantharidin-alters-the-expression-of-genes-associated-with-the-nkg2d-associated-immune-response-in-tsgh-8301-human-bladder-carcinoma-cells
#3
Jehn-Hwa Kuo, An-Cheng Huang, Jen-Jyh Lin, Kuang-Chi Lai, Rick Sai-Chuen Wu, Jiun-Long Yang, Bin-Chuan Ji, Mei-Due Yang, Yung-Lin Chu, Jing-Gung Chung
Cantharidin (CTD) is a natural toxin in beetles of the Mylabris genus (blister beetle), which has been revealed to induce cell death in various types of human cancer cells. However, to the best of our knowledge, no previous studies have investigated the effect of CTD on the expression of genes and their associated signaling pathways in human bladder carcinoma cells. In the present study, CTD-induced cell morphological changes and apoptosis were observed using phase-contrast microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively, in TSGH-8301 human bladder carcinoma cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28690853/significantly-enhanced-lung-metastasis-and-reduced-organ-nk-cell-functions-in-diet-induced-obese-rats
#4
J Spielmann, J Hanke, D Knauf, S Ben-Eliyahu, R Jacobs, G I Stangl, I Bähr, H Kielstein
BACKGROUND: Obesity was identified as a major risk factor for malignant diseases, but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal aspect of innate immunity, are capable of identifying and killing virally infected and tumor cells. Previous studies have shown altered NK cell functions in obesity, and the current study aimed to investigate the relationship between altered NK cell functions and increased cancer risk in obesity. METHODS: To induce obesity male F344-rats received a high-fat diet (34% fat) or a control diet (4% fat)...
2017: BMC Obesity
https://www.readbyqxmd.com/read/28689087/the-histone-deacetylase-inhibitor-saha-simultaneously-reactivates-hiv-1-from-latency-and-up-regulates-nkg2d-ligands-sensitizing-for-natural-killer-cell-cytotoxicity
#5
Maria Giovanna Desimio, Erica Giuliani, Margherita Doria
In pilot HIV-1 eradication studies, patients' immune responses were ineffective at killing viral reservoirs reactivated through latency reversing agents (LRAs) like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using latently HIV-1-infected J-Lat 6.3/8.4/9...
July 6, 2017: Virology
https://www.readbyqxmd.com/read/28684217/nkg2d-ligand-expression-in-crohn-s-disease-and-nkg2d-dependent-stimulation-of-cd8-t-cell-migration
#6
Kasper Vadstrup, Elisabeth Douglas Galsgaard, Helle Jensen, Lewis L Lanier, James C Ryan, Shih-Yu Chen, Garry P Nolan, Marianne Kajbæk Vester-Andersen, Julie Steen Pedersen, Jens Gerwien, Teis Jensen, Flemming Bendtsen
Interaction between the activating NKG2D receptor on lymphocytes and its ligands MICA, MICB, and ULBP1-6 modulate T and NK cell activity and may contribute to the pathogenesis of Crohn's disease (CD). NKG2D ligands are generally not expressed on the cell surface of normal, non-stressed cells, but expression of MICA and MICB in CD intestine has been reported. In this exploratory study, we further characterize the expression of NKG2D and its ligands, including the less well-described ULBP4-6, in CD, and test if NKG2D ligand interactions are involved in the migration of activated T cells into the affected mucosal compartments...
July 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#7
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680742/modulation-of-mhc-class-i-surface-expression-in-b16f10-melanoma-cells-by-methylseleninic-acid
#8
Claudia Lennicke, Jette Rahn, Jürgen Bukur, Falko Hochgräfe, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28677817/inhibition-of-the-hdac-suv39-g9a-pathway-restores-the-expression-of-dna-damage-dependent-major-histocompatibility-complex-class%C3%A2-i-related-chain%C3%A2-a%C3%A2-and%C3%A2-b-in-cancer-cells
#9
Nakako Izumi Nakajima, Atsuko Niimi, Mayu Isono, Takahiro Oike, Hiro Sato, Takashi Nakano, Atsushi Shibata
Immunotherapy is expected to be promising as a next generation cancer therapy. Immunoreceptors are often activated constitutively in cancer cells, however, such levels of ligand expression are not effectively recognized by the native immune system due to tumor microenvironmental adaptation. Studies have demonstrated that natural-killer group 2, member D (NKG2D), a major activating immunoreceptor, responds to DNA damage. The upregulation of major histocompatibility complex class I-related chain A and B (MICA/B) (members of NKG2D ligands) expression after DNA damage is associated with NK cell-mediated killing of cancer cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28673007/cytokine-induced-killer-cell-therapy-for-modulating-regulatory-t-cells-in-patients-with-non-small-cell-lung-cancer
#10
Baodan Yu, Junli Wang, Chen He, Wei Wang, Jianli Tang, Runhui Zheng, Chengzhi Zhou, Huanhuan Zhang, Zhiping Fu, Qiasheng Li, Jun Xu
Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28659311/memory-t-cells-expressing-an-nkg2d-car-efficiently-target-osteosarcoma-cells
#11
Lucía Fernández, Jean-Yves Metais, Adela Escudero, Maria Vela, Jaime Valentín, Isabel Vallcorba, Alejandra Leivas, Juan Torres, Antonio Valeri, Ana Patiño-García, Joaquín Martínez-López, Wing Leung, Antonio Pérez-Martínez
NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK cell elimination of osteosarcoma tumor initiating cells. In this report, we used NKG2D-NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA- memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR)...
June 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28655861/in-silico-modeling-identifies-cd45-as-a-regulator-of-il-2-synergy-in-the-nkg2d-mediated-activation-of-immature-human-nk-cells
#12
Sayak Mukherjee, Helle Jensen, William Stewart, David Stewart, William C Ray, Shih-Yu Chen, Garry P Nolan, Lewis L Lanier, Jayajit Das
Natural killer (NK) cells perform immunosurveillance of virally infected and transformed cells, and their activation depends on the balance between signaling by inhibitory and activating receptors. Cytokine receptor signaling can synergize with activating receptor signaling to induce NK cell activation. We investigated the interplay between the signaling pathways stimulated by the cytokine interleukin-2 (IL-2) and the activating receptor NKG2D in immature (CD56(bright)) and mature (CD56(dim)) subsets of human primary NK cells using mass cytometry experiments and in silico modeling...
June 27, 2017: Science Signaling
https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#13
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28636546/changes-of-peripheral-lymphocyte-subsets-and-cytokine-environment-during-ageing-and-deteriorating-gastrointestinal-tract-health-status
#14
Jing Wang, Guodong Yang, Dongfang Wang, Kuiliang Liu, Yongchao Ma, Hong Liu, Jing Wu, Min Fang
Human immune senescence accompanies with the physical and physiological frailty. The functional change and shift of NK, NKT and T cell subsets by ageing have been widely studied. However, it remains largely unclear how the ageing and disease conditions affect the distribution of lymphocytes. In the present study, 233 subjects with age range from 20 to 87 year old, including healthy people, people with chronic gastrointestinal tract disease or cancers were investigated. We found that the proportion of NK cells, CD8+ T cells and NKT cells remained relatively unchanged with ageing...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#15
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628025/-phenotype-facilities-of-lymphocytes-in-hemorrhagic-fever-with-renal-syndrome
#16
M Ivanov, I Balmasova, Z Vasnyova
Hemorrhagic fever with renal syndrome (HFRS) is a feral herd disease caused by hantaviruses. HERS may be severe and its manifestations include acute renal failure, intoxication, hemorrhages and pain syndrome. Hantaviruses as pathogen of HFRS wield considerable influence on the character of the immune response, in particular, is capable of lymphocytic cytolysis suppressing. It was found that cytotoxic T lymphocytes along with NKT and CD8 + regulatory T cells play the key role in the immune mechanisms of hemorrhagic fever with renal syndrome...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28622272/nk-cell-derived-exosomes-from-nk-cells-previously-exposed-to-neuroblastoma-cells-augment-the-antitumor-activity-of-cytokine-activated-nk-cells
#17
Alireza Shoae-Hassani, Amir Ali Hamidieh, Maryam Behfar, Rashin Mohseni, Seyed A Mortazavi-Tabatabaei, Shahab Asgharzadeh
Immune cell-derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells...
June 15, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28617830/on-treatment-decrease-of-nkg2d-correlates-to-early-emergence-of-clinically-evident-hepatocellular-carcinoma-after-interferon-free-therapy-for-chronic-hepatitis-c
#18
Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Ugamura, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai
BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i...
2017: PloS One
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#19
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#20
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
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