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Nk cell activation

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https://www.readbyqxmd.com/read/29453519/tricurin-a-synergistic-formulation-of-curcumin-resveratrol-and-epicatechin-gallate-repolarizes-tumor-associated-macrophages-and-triggers-an-immune-response-to-cause-suppression-of-hpv-tumors
#1
Sumit Mukherjee, Rahman Hussaini, Richard White, Doaa Atwi, Angela Fried, Samay Sampat, Longzhu Piao, Quintin Pan, Probal Banerjee
Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29452720/evaluation-of-the-biological-activities-of-the-il-15-superagonist-complex-alt-803-following-intravenous-versus-subcutaneous-administration-in-murine-models
#2
Bai Liu, Monica Jones, Lin Kong, Terra Noel, Emily K Jeng, Sixiang Shi, Christopher G England, Sarah Alter, Jeffrey S Miller, Weibo Cai, Peter R Rhode, Hing C Wong
ALT-803 is a fusion protein complex consisting of an interleukin (IL)-15 superagonist and a dimeric IL-15 receptor alpha sushi domain IgG1 Fc fusion protein. When administered to mice, ALT-803 is capable of inducing natural killer (NK) and CD8 + T cell proliferation and activation, and effectively promoting potent anti-tumor responses. Currently, ALT-803 is in clinical trials for treatment of various solid tumors and hematological malignancies. In the initial phase of these clinical studies, intravenous (iv) injection was used according to the route used in pre-clinical efficacy studies...
February 13, 2018: Cytokine
https://www.readbyqxmd.com/read/29449322/actin-retrograde-flow-controls-natural-killer-cell-response-by-regulating-the-conformation-state-of-shp-1
#3
Omri Matalon, Aviad Ben-Shmuel, Jessica Kivelevitz, Batel Sabag, Sophia Fried, Noah Joseph, Elad Noy, Guy Biber, Mira Barda-Saad
Natural killer (NK) cells are a powerful weapon against viral infections and tumor growth. Although the actin-myosin (actomyosin) cytoskeleton is crucial for a variety of cellular processes, the role of mechanotransduction, the conversion of actomyosin mechanical forces into signaling cascades, was never explored in NK cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the immune response of primary human NK cells through a novel interaction between β-actin and the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1), converting its conformation state, and thereby regulating NK cell cytotoxicity...
February 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29449276/immune-evasion-via-pd-1-pd-l1-on-nk-cells-and-monocyte-macrophages-is-more-prominent-in-hodgkin-lymphoma-than-dlbcl
#4
Frank Vari, David Arpon, Colm Keane, Mark S Hertzberg, Dipti Talaulikar, Sanjiv Jain, Qingyan Cui, Erica Han, Josh Tobin, Robert Bird, Donna Cross, Annette Hernandez, Clare Gould, Simone Birch, Maher K Gandhi
Much focus has been on the interaction of PD-L1 on malignant B-cells with PD-1 on effector T-cells in inhibiting anti-lymphoma immunity. We sought to establish the contribution of NK-cells and inhibitory CD163 + monocytes/macrophages in Hodgkin Lymphoma (cHL) and Diffuse Large B-cell Lymphoma (DLBCL). Levels of PD-1 on NK-cells were elevated in cHL relative to DLBCL. Notably, CD3 - CD56 hi CD16 -ve NK-cells had substantially higher PD-1 expression relative to CD3 - CD56 dim CD16 + cells, and were expanded in blood and tissue, more marked in cHL than DLBCL patients...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29449224/natural-killer-receptor-ligand-expression-on-acute-myeloid-leukemia-impacts-survival-and-relapse-after-chemotherapy
#5
Sara Mastaglio, Eric Wong, Travis Perera, Jane Ripley, Piers Blombery, Mark J Smyth, Rachel Koldej, David Ritchie
Natural killer (NKs) cells provide rapid responses to viral-infected and malignant cells, including acute myeloid leukemia (AML) blasts. The balance among inhibitory and activating signals, delivered by multiple interactions between ligands on target cells and NK receptors, determines the posture of the NK cell response to either one of target cell elimination or tolerance. The aim of this work was to study the influence of the differential expression of activating and inhibitory NK receptor ligands (NKRLs) by leukemic blasts on clinical outcome in newly diagnosed AML patients...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29447423/nk-cells-inhibit-anti-m-bovis-bcg-t-cell-responses-and-aggravate-pulmonary-inflammation-in-a-direct-lung-infection-mouse-model
#6
Dongfang Wang, Xiuling Gu, Xiaoman Liu, Songtao Wei, Bin Wang, Min Fang
Tuberculosis remains a threat to public health. The major problem for curing this disease is latent infection, of which the underlying mechanisms are still not fully understood. Previous studies indicate that NK cells do not play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung, and recent studies have revealed that NK cells regulate the adaptive immunity during mycobacterial infection. By using a mouse model of direct lung infection with M.bovis BCG, we found that the presence of NK cells postponed the priming and activation of T cells after BCG infection...
February 15, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29447367/endometrial-natural-killer-nk-cells-reveal-a-tissue-specific-receptor-repertoire
#7
D Feyaerts, T Kuret, B van Cranenbroek, S van der Zeeuw-Hingrez, O W H van der Heijden, A van der Meer, I Joosten, R G van der Molen
STUDY QUESTION: Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? SUMMARY ANSWER: The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. WHAT IS KNOWN ALREADY: NK cells are important for successful pregnancy...
February 13, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29447242/a-novel-ligand-on-astrocytes-interacts-with-natural-cytotoxicity-receptor-nkp44-regulating-immune-response-mediated-by-nk-cells
#8
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
https://www.readbyqxmd.com/read/29446443/association-of-killer-cell-immunoglobulin-like-receptors-with-spontaneous-clearance-of-hepatitis-c-virus-in-the-chinese-population
#9
Zhengang Shan, Jieting Huang, Qiao Liao, Ke Huang, Min Wang, Ru Xu, Xi Tang, Weiyun Zhang, Kenrad Nelson, Yongshui Fu, Chengyao Li, Xia Rong
BACKGROUND: Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection...
February 15, 2018: Transfusion
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#10
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444897/role-of-nkp46-natural-killer-cells-in-house-dust-mite-driven-asthma
#11
Eline Haspeslagh, Mary J van Helden, Kim Deswarte, Sofie De Prijck, Justine van Moorleghem, Louis Boon, Hamida Hammad, Eric Vivier, Bart N Lambrecht
House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69 + NK cells in the bronchoalveolar lumen...
February 14, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29440510/educated-natural-killer-cells-show-dynamic-movement-of-the-activating-receptor-nkp46-and-confinement-of-the-inhibitory-receptor-ly49a
#12
Elina Staaf, Per Niklas Hedde, Sunitha Bagawath Singh, Joachim Piguet, Enrico Gratton, Sofia Johansson
Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education has so far not been fully described. In addition, distinctive phenotypic markers of educated NK cells at the single-cell level are lacking. We developed a refined version of the image mean square displacement (iMSD) method (called iMSD carpet analysis) and used it in combination with single-particle tracking to characterize the dynamics of the activating receptor NKp46 and the inhibitory receptor Ly49A on resting educated versus hyporesponsive murine NK cells...
February 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29438058/assessment-of-antibody-dependent-cellular-cytotoxicity-by-flow-cytometry
#13
Thomas D Duensing, Susan R Watson
A useful feature of therapeutic antibodies is the ability to kill the cells to which they bind. Antibodies are capable of mediating cell killing in a variety of ways. Apoptosis, complement-mediated mechanisms, and antibody-dependent cellular cytotoxicity (ADCC) are all effects that can be assayed to characterize lead antibody candidates. Extensive, multidose characterizations of a series of candidates can be performed in a short amount of time using assays developed for high-throughput flow cytometry systems...
February 1, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29437230/lectin-isolated-from-japanese-red-sword-beans-canavalia-gladiata-as-a-potential-cancer-chemopreventive-agent
#14
Satsuki Une, Koji Nonaka, Junich Akiyama
In this study, we investigated the chemical and biological profile of lectin isolated from Japanese red sword beans (Canavalia gladiata; RSBs). RSB lectin was purified using maltamyl-Sepharose 4B and subjected to amino acid composition and partial amino acid sequencing analyses, and evaluated for blood and carbohydrate specificity, mitogenic activity, splenic natural killer (NK) cell activity, and its effect on B16 melanoma cell proliferation, compared with Concanavalin A (Con A). The amino acid composition and sequences of RSB lectin were similar to those of Con A...
February 13, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29434608/a-case-of-type-2-hypersensitivity-to-rasburicase-diagnosed-with-a-natural-killer-cell-activation-assay
#15
Sébastien Viel, Rémi Pescarmona, Alexandre Belot, Audrey Nosbaum, Christine Lombard, Thierry Walzer, Frédéric Bérard
Drug hypersensitivity reactions can lead to different clinical pictures depending on the underlying immunological mechanism. Diagnosis tests are already available to assess the most frequent drugs hypersensitivity reactions, which are mediated by specific IgE or T cells. However, it remains challenging to diagnose type 2 hypersensitivity reactions (T2HR), which can lead to severe cytopenia and liver failure. Here, we describe a case of T2HR to rasburicase, an uricolytic agent used to prevent tumor lysis syndrome...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29434597/92r-monoclonal-antibody-inhibits-human-ccr9-leukemia-cells-growth-in-nsg-mice-xenografts
#16
Beatriz Somovilla-Crespo, Maria Teresa Martín Monzón, Maria Vela, Isabel Corraliza-Gorjón, Silvia Santamaria, Jose A Garcia-Sanz, Leonor Kremer
CCR9 is as an interesting target for the treatment of human CCR9+-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433450/pathogen-recognition-by-nk-cells-amplifies-the-pro-inflammatory-cytokine-production-of-monocyte-derived-dc-via-ifn-%C3%AE
#17
Tammy Oth, Thomas H P M Habets, Wilfred T V Germeraad, Marijke I Zonneveld, Gerard M J Bos, Joris Vanderlocht
BACKGROUND: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus...
February 13, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#18
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29428349/clarity-bpa-effects-of-chronic-bisphenol-a-exposure-on-the-immune-system-part-1-quantification-of-the-relative-number-and-proportion-of-leukocyte-populations-in-the-spleen-and-thymus
#19
Jinpeng Li, Anthony Bach, Robert B Crawford, Ashwini S Phadnis-Moghe, Weimin Chen, Shawna D'Ingillo, Natalia Kovalova, Jose E Suarez-Martinez, Jiajun Zhou, Barbara L F Kaplan, Norbert E Kaminski
Bisphenol A (BPA) is extensively used in manufacturing of a broad range of consumer products worldwide. Due to its widespread use, human exposure to BPA is virtually ubiquitous. Broad human exposure coupled with a large scientific literature describing estrogenic activity of BPA in animals has raised public health concerns. To comprehensively evaluate the health effects of BPA exposure, a chronic toxicity study using a wide-range of BPA doses (2.5-25000 μg/kg bw/day) was conducted jointly by the NTP, thirteen NIEHS-supported grantees, and the FDA, which is called the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA)...
February 8, 2018: Toxicology
https://www.readbyqxmd.com/read/29427786/clarity-bpa-effects-of-chronic-bisphenol-a-exposure-on-the-immune-system-part-2-characterization-of-lymphoproliferative-and-immune-effector-responses-by-splenic-leukocytes
#20
Jinpeng Li, Anthony Bach, Robert B Crawford, Ashwini S Phadnis-Moghe, Weimin Chen, Shawna D'Ingillo, Natalia Kovalova, Jose E Suarez-Martinez, Jiajun Zhou, Barbara L F Kaplan, Norbert E Kaminski
Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory...
February 7, 2018: Toxicology
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