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Nk cell activation

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https://www.readbyqxmd.com/read/28733594/cd56-is-a-pathogen-recognition-receptor-on-human-natural-killer-cells
#1
Sabrina Ziegler, Esther Weiss, Anna-Lena Schmitt, Jan Schlegel, Anne Burgert, Ulrich Terpitz, Markus Sauer, Lorenzo Moretta, Simona Sivori, Ines Leonhardt, Oliver Kurzai, Hermann Einsele, Juergen Loeffler
Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732438/investigation-of-killer-immunoglobulin-like-receptor-kir-and-hla-genotypes-to-predict-the-occurrence-of-acute-allograft-rejection-after-kidney-transplantation
#2
Davood Jafari, Mohsen Nafar, Mir Saeed Yekaninejad, Razieh Abdolvahabi, Mahboob Lesan Pezeshki, Efat Razaghi, Ali Akbar Amirzargar
After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR)...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#3
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28726600/age-and-sex-associated-differences-in-phenotypic-and-functional-characteristics-of-peripheral-blood-lymphocytes-in-chimpanzees-pan-troglodytes
#4
Pramod Nehete, Elizabeth Magden, Bharti Nehete, Lawrence Williams, Christian Abee, K Sastry
Chimpanzees are the closest phylogenetic relatives to humans, sharing more than 98% genetic sequence identity. Thesegenetic similarities prompted the belief that chimpanzees can serve as an ideal model for human disease conditions andvaccine development. However, in light of the recent NIH decision to phase out biomedical research in chimpanzees and retire NIH-supported chimpanzees, data from the present study will continue to provide value for the care of aged and sick chimpanzees located in zoos, sanctuaries, and primate centers...
July 19, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#5
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28725030/a-practical-model-evaluating-antiviral-cytokines-by-natural-killer-cells-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b-virus-infection
#6
Xiaoyan Li, Yurong Gu, Xiaobo Guo, Lin Gu, Liang Zhou, Xiaojuan Wu, Xueqin Wang, Zania Stamataki, Yuehua Huang
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#7
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724544/mica-expressing-monocytes-enhance-natural-killer-cell-fc-receptor-mediated-antitumor-functions
#8
Amanda R Campbell, Megan C Duggan, Lorena P Suarez-Kelly, Neela Bhave, Kallan S Opheim, Elizabeth McMichael, Prashant Trikha, Robin Parihar, Eric Luedke, Adrian Lewis, Bryant Yung, Robert Lee, David Raulet, Susheela Tridandapani, Veronika Groh, Lianbo Yu, Vedat Yildiz, John C Byrd, Michael A Caligiuri, William E Carson
Natural Killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNgamma, MIP-1alpha, TNFalpha) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as interleukin (IL) 12. We now demonstrate that this response is enhanced in the presence of autologous monocytes...
July 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28723565/the-transcription-factor-tcf1-contributes-to-normal-nk-cell-development-and-function-by-limiting-the-expression-of-granzymes
#9
Beena Jeevan-Raj, Jasmine Gehrig, Mélanie Charmoy, Vijaykumar Chennupati, Camille Grandclément, Paolo Angelino, Mauro Delorenzi, Werner Held
The transcription factor Tcf1 is essential for the development of natural killer (NK) cells. However, its precise role has not been clarified. Our combined analysis of Tcf1-deficient and transgenic mice indicated that Tcf1 guides NK cells through three stages of development. Tcf1 expression directed bone marrow progenitors toward the NK cell lineage and ensured the survival of NK-committed cells, and its downregulation was needed for terminal maturation. Impaired survival of NK-committed cells was due to excessive expression of granzyme B (GzmB) and other granzyme family members, which induced NK cell self-destruction during maturation and following activation with cytokines or target cells...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723548/the-fc-domain-of-immunoglobulin-is-sufficient-to-bridge-nk-cells-with-virally-infected-cells
#10
Hong-Sheng Dai, Nathaniel Griffin, Chelsea Bolyard, Hsiaoyin Charlene Mao, Jianying Zhang, Timothy P Cripe, Tadahiro Suenaga, Hisashi Arase, Ichiro Nakano, E A Chiocca, Balveen Kaur, Jianhua Yu, Michael A Caligiuri
Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722018/a-pro-survival-role-for-the-intracellular-granzyme-b-inhibitor-serpinb9-in-natural-killer-cells-during-poxvirus-infection
#11
Matthew S Mangan, Carolina R Melo-Silva, Jennii Luu, Catherina H Bird, Aulikki Koskinen, Alexandra Rizzitelli, Monica Prakash, Katrina L Scarff, Arno Müllbacher, Matthias Regner, Phillip I Bird
Intracellular serpins are proposed to inactivate proteases released from lysosome-related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B-mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature NK cells, and activated CD8(+) T cells...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721573/exposure-to-silver-nanoparticles-affects-viability-and-function-of-natural-killer-cells-mostly-via-the-release-of-ions
#12
Loretta Müller, Selina K Steiner, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Barbara Rothen-Rutishauser, Philipp Latzin
Natural killer (NK) cells play a crucial role in linking innate and adaptive immune responses, especially during viral infections and tumor surveillance. They have two major effector functions: the killing of stressed/abnormal cells and the release of cytokines. Their activity is regulated via inhibitory and activating surface receptors. At the same time that the production and use of engineered nanoparticles is steadily increasing, the risk for exposure to silver nanoparticles (AgNPs) from consumer products or biomedical applications is growing...
July 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28720772/blockade-of-axl-signaling-ameliorates-hpv16e6-mediated-tumorigenecity-of-cervical-cancer
#13
Eun-Hee Lee, Kon-Young Ji, Eun-Mi Kim, Su-Man Kim, Hyeong-Woo Song, Ha-Rim Choi, Byung Yeoup Chung, Hyo Jin Choi, Hyoung-Woo Bai, Hyung-Sik Kang
Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718997/mesenchymal-stem-cell-derived-factors-immuno-modulatory-effects-and-therapeutic-potential
#14
REVIEW
Vladislav Volarevic, Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Valentin Djonov, Nebojsa Arsenijevic
Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28717244/trail-regulatory-receptors-constrain-human-hepatic-stellate-cell-apoptosis
#15
Harsimran D Singh, Itziar Otano, Krista Rombouts, Kasha P Singh, Dimitra Peppa, Upkar S Gill, Katrin Böttcher, Patrick T F Kennedy, Jude Oben, Massimo Pinzani, Henning Walczak, Giuseppe Fusai, William M C Rosenberg, Mala K Maini
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716751/rehmannia-glutinosa-polysaccharide-induced-an-anti-cancer-effect-by-activating-natural-killer-cells
#16
Li Xu, Wei Zhang, Ling Zeng, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has exhibited an immune stimulatory effect, such as dendritic cell activation, but it has not been studied in terms of the activation capacity of natural killer (NK) cells in mice in vivo. In this study, we examined the effect of RGP on the proliferation and activation of NK cells in the spleen, mesenteric lymph node (mLN), and blood in vivo and compared that function with that of Escherichia coli lipopolysaccharide. The administration of RGP to C57BL/6 mice induced the increase in circulating blood NK cell numbers and in the proliferation of NK cells in the spleen, mLN, and blood...
July 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28715416/signatures-of-inflammation-and-impending-multiple-organ-dysfunction-in-the-hyperacute-phase-of-trauma-a-prospective-cohort-study
#17
Claudia P Cabrera, Joanna Manson, Joanna M Shepherd, Hew D Torrance, David Watson, M Paula Longhi, Mimoza Hoti, Minal B Patel, Michael O'Dwyer, Sussan Nourshargh, Daniel J Pennington, Michael R Barnes, Karim Brohi
BACKGROUND: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28714406/role-of-the-immune-component-of-tumor-microenvironment-in-the-efficiency-of-cancer-treatment-perspectives-for-the-personalized-therapy
#18
Marina Stakheyeva, Vladimir Riabov, Irina Mitrofanova, Nikolai Litviakov, Evgeny Choynzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714337/correlation-between-natural-killer-cell-activity-and-systemic-inflammatory-markers-for-heterogeneous-cancer-patients-treated-with-wheel-balance-cancer-therapy
#19
Hwi-Joong Kang, Kyeore Bae, Jee-Hye Kim, Chong-Kwan Cho, Hwa-Seung Yoo
BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT)...
July 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28713379/op9-feeder-cells-are-superior-to-m2-10b4-cells-for-the-generation-of-mature-and-functional-natural-killer-cells-from-umbilical-cord-hematopoietic-progenitors
#20
Lara Herrera, Juan Manuel Salcedo, Silvia Santos, Miguel Ángel Vesga, Francisco Borrego, Cristina Eguizabal
Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB) CD34(+) hematopoietic stem cells (HSCs), mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56(+) NK cells from UCB CD34(+) HSC...
2017: Frontiers in Immunology
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