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Natural Killer Cell

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https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#1
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29775592/dietary-and-microbial-oxazoles-induce-intestinal-inflammation-by-modulating-aryl-hydrocarbon-receptor-responses
#2
Shankar S Iyer, Thomas Gensollen, Amit Gandhi, Sungwhan F Oh, Joana F Neves, Frederic Collin, Richard Lavin, Carme Serra, Jonathan Glickman, Punyanganie S A de Silva, R Balfour Sartor, Gurdyal Besra, Russell Hauser, Anthony Maxwell, Amadeu Llebaria, Richard S Blumberg
Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs)...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29774968/granulysin-mediated-apoptosis-of-trophoblasts-in-blighted-ovum-and-missed-abortion
#3
Tamara Gulic, Gordana Laskarin, Marin Dominovic, Lana Glavan Gacanin, Emina Babarović, Zeljka Rubesa, Herman Haller, Daniel Rukavina
PROBLEM: Granulysin (GNLY) is a cytotoxic molecule mostly present in decidual natural killer (NK) cells. Blighted ovum (BO) and missed abortion (MA) represent the early pathological pregnancies with hindered development of the embryoblast or a dead embryo. We investigated the GNLY-mediated apoptotic mechanism potentially responsible for delayed termination of pregnancy. METHOD OF STUDY: We performed immunohistological and immunofluorescence labeling of decidual tissues (GNLY, Apaf-1, NF-κB)...
May 18, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#4
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29773448/the-role-of-the-common-gamma-chain-family-cytokines-in-%C3%AE-%C3%AE-t-cell-based-anti-cancer-immunotherapy
#5
REVIEW
Heleen H Van Acker, Diana Campillo-Davo, Gils Roex, Maarten Versteven, Evelien L Smits, Viggo F Van Tendeloo
Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anti-cancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (γδ) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade...
May 14, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29770131/real-time-tracking-of-ex-vivo-expanded-natural-killer-cells-toward-human-triple-negative-breast-cancers
#6
Tung Nguyen Thanh Uong, Kyung-Hwa Lee, Sung-Ja Ahn, Kyung Won Kim, Jung-Joon Min, Hoon Hyun, Mee Sun Yoon
Introduction: Ex vivo -expanded natural killer (NK) cells are a potential candidate for cancer immunotherapy based on high cytotoxicity against malignant tumor cells. However, a limited understanding of the migration of activated NK cells toward solid tumors is a critical dilemma in the development of effective and adoptive NK cell-based immunotherapy. Methods: Ex vivo -expanded NK cells from healthy donors were stained with near-infrared fluorophores at different concentrations...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769573/discovery-of-a-novel-il-15-based-protein-with-improved-developability-and-efficacy-for-cancer-immunotherapy
#7
Qiyue Hu, Xin Ye, Xiangdong Qu, Dongbing Cui, Lei Zhang, Zhibin Xu, Hong Wan, Lianshan Zhang, Weikang Tao
Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+ /CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768178/trained-memory-of-human-uterine-nk-cells-enhances-their-function-in-subsequent-pregnancies
#8
Moriya Gamliel, Debra Goldman-Wohl, Batya Isaacson, Chamutal Gur, Natan Stein, Rachel Yamin, Michael Berger, Myriam Grunewald, Eli Keshet, Yoach Rais, Chamutal Bornstein, Eyal David, Adam Jelinski, Iris Eisenberg, Caryn Greenfield, Arbel Ben-David, Tal Imbar, Ronit Gilad, Ronit Haimov-Kochman, David Mankuta, Matan Elami-Suzin, Ido Amit, Jacob H Hanna, Simcha Yagel, Ofer Mandelboim
Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs)...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29767843/how-i-treat-primary-haemophagocytic-lymphohistiocytosis
#9
REVIEW
Rebecca A Marsh, Elie Haddad
Primary haemophagocytic lymphohistiocytosis (HLH) diseases are a collection of inherited genetic disorders that cause the syndrome of HLH. Great advances have been made in the last 20 years with regard to the discovery of many of the genetic aetiologies of disease. Several advances have also been made on the clinical stage. Accurate screening diagnostics for primary HLH diseases that are superior to traditional Natural Killer cell function testing have been developed and are now available in many countries...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#10
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/29764843/poorly-cytotoxic-terminally-differentiated-cd56-neg-cd16-pos-nk-cells-accumulate-in-kenyan-children-with-burkitt-lymphomas
#11
Catherine S Forconi, Cormac P Cosgrove, Pryia Saikumar-Lakshmi, Christina E Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A Otieno, Galit Alter, Christian Münz, Ann M Moormann
Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29764519/plasmodium-yoelii-infection-inhibits-murine-leukaemia-wehi-3-cell-proliferation-in-vivo-by-promoting-immune-responses
#12
Zhen-Zhen Tong, Zheng-Ming Fang, Qi Zhang, Yun Zhan, Yue Zhang, Wan-Fang Jiang, Xiao Hou, Yong-Long Li, Ting Wang
BACKGROUND: Leukaemia is a malignant leukocyte disorder with a high fatality rate, and current treatments for this disease are unsatisfactory. Therefore, new therapeutic strategies for leukaemia must be developed. Malaria parasite infection has been shown to be effective at combating certain neoplasms in animal experiments. This study is to demonstrate the anti-leukaemia activity of malaria parasite Plasmodium yoelii (P. yoelii) infection,. METHODS: In this study, the proportion of CD3, CD19, CD11b and Mac-3 cells was analysed by flow cytometry; the levels of IFN-γ and TNF-α in individual serum samples were measured by enzyme-linked immunosorbent assay, and the phagocytic activity of macrophages and natural killer (NK) cell activity were measured by flow cytometry...
May 16, 2018: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29764159/emerging-role-of-immunotherapy-for-childhood-cancers
#13
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29764116/circulating-low-absolute-cd4-t-cell-counts-may-predict-poor-prognosis-in-extranodal-nk-t-cell-lymphoma-patients-treating-with-pegaspargase-based-chemotherapy
#14
Ya-Ping Zhang, Run Zhang, Hua-Yuan Zhu, Li Wang, Yu-Jie Wu, Jin-Hua Liang, Wen-Yu Shi, Hong Liu, Wei Xu, Jian-Yong Li
Purpose: Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. Materials and Methods: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens...
May 14, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29760798/a-multicenter-retrospective-comparison-of-sequential-versus-sandwich-chemoradiotherapy-for-stage-ie-iie-extranodal-natural-killer-t-cell-lymphoma-nasal-type
#15
Jin Li, Yajun Li, Meizuo Zhong, Wei Liu, Xianling Liu, Jiwei Li, Kunlun Li, Pingyong Yi
Background: Chemotherapy and radiotherapy are critical for treating early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL); however, the optimal therapy sequence remains unclear. Therefore, we performed this study to compare the efficacy of L-asparaginase/pegaspargase-based sequential versus sandwich chemoradiotherapy for patients newly diagnosed with stage IE-IIE ENKTL. Methods: Patients were categorized into sequential ( N = 111) and sandwich ( N = 104) groups. Chemotherapy regimens included GELOX, SMILE, and VLP...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29760706/complement-opsonized-hiv-1-alters-cross-talk-between-dendritic-cells-and-natural-killer-nk-cells-to-inhibit-nk-killing-and-to-upregulate-pd-1-cxcr3-and-ccr4-on-t-cells
#16
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760699/tetraspanin-cd9-a-key-regulator-of-cell-adhesion-in-the-immune-system
#17
REVIEW
Raquel Reyes, Beatriz Cardeñes, Yesenia Machado-Pineda, Carlos Cabañas
The tetraspanin CD9 is expressed by all the major subsets of leukocytes (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, granulocytes, monocytes and macrophages, and immature and mature dendritic cells) and also at a high level by endothelial cells. As a typical member of the tetraspanin superfamily, a prominent feature of CD9 is its propensity to engage in a multitude of interactions with other tetraspanins as well as with different transmembrane and intracellular proteins within the context of defined membranal domains termed tetraspanin-enriched microdomains (TEMs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760540/ambiguous-roles-of-innate-lymphoid-cells-in-chronic-development-of-liver-diseases
#18
REVIEW
Yue Shen, Jing Li, Si-Qi Wang, Wei Jiang
Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17...
May 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29760342/1-2-3-triazolyl-ester-of-ketorolac-15k-boosting-both-heat-endurance-and-lifespan-of-c-elegans-by-down-regulating-pak1-at-nm-levels
#19
Binh C Nguyen, Sung-A Kim, Seong-Min Won, Sang-Kyu Park, Yoshihiro Uto, Hiroshi Maruta
PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C...
2018: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/29757593/severe-combined-immunodeficiency-a-case-series-and-review-from-a-tertiary-pediatric-hospital
#20
Shahrzad Fallah, Mehrnaz Mesdaghi, Mahboubeh Mansouri, Delara Babaei, Abdollah Karimi, Seyed Alireza Fahimzad, Shahnaz Armin, Sedigheh Rafiei Tabatabaei, Roxana Azma, Ghamartaj Khanbabaee, Bahram Bashardoost, Mehrdad Amirmoeini, Saeed Sadr, Rozita Jalilianhasanpour, Roxana Ghanaei, Nima Rezaei, Zahra Chavoshzadeh
Severe combined immunodeficiency syndrome (SCID) is a life-threatening condition leading to early infant death as a result of severe infection, due to impaired cellular and humoral immune systems. Various forms of SCID are classified based on the presence or absence of T cells, B cells and natural killer cells. Patients usually present with recurrent infections and failure to thrive. Definitive treatment is hematopoietic stem cell transplantation. To achieve the best outcome, it should be performed prior to the development of severe infection...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
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