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https://www.readbyqxmd.com/read/29042994/immunological-mechanism-of-low-dose-priming-radiation-resistance-in-walker-256-tumor-model-mice
#1
Li Feng, Ling Qin, Dan Guo, Daping Deng, Feng Lu, Hailiang Li, Narisu Bao, Xiting Yang, Hongyu Ding, Jianguo Li
The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042488/natural-killer-cells-mediate-pathophysiology-in-response-to-reduced-uterine-perfusion-pressure
#2
Jamil Elfarra, Lorena M Amaral, Maggie McCalmon, Jeremy D Scott, Mark W Cunningham, Ashley Gnam, Tarek Ibrahim, Babbette LaMarca, Denise C Cornelius
Preeclampsia is associated with hypertension, small-for-gestational-age babies and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia...
October 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#3
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29040754/development-of-unique-cytotoxic-chimeric-antigen-receptors-based-on-human-scfv-targeting-b7h6
#4
Casey K Hua, Albert T Gacerez, Charles L Sentman, Margaret E Ackerman
As a stress-inducible natural killer (NK) cell ligand, B7H6 plays a role in innate tumor immunosurveillance and is a fairly tumor selective marker expressed on a variety of solid and hematologic cancer cells. Here, we describe the isolation and characterization of a new family of single chain fragment variable (scFv) molecules targeting the human B7H6 ligand. Through directed evolution of a yeast surface displayed non-immune human-derived scFv library, eight candidates comprising a single family of clones differing by up to four amino acid mutations and exhibiting nM avidities for soluble B7H6-Ig were isolated...
October 11, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29038620/dengue-virus-induces-nk-cell-activation-through-trail-expression-during-infection
#5
Mariana Gandini, Fabienne Petitinga-Paiva, Cíntia Ferreira Marinho, Gladys Correa, Luzia Maria De Oliveira-Pinto, Luiz José de Souza, Rivaldo Venâncio Cunha, Claire Fernandes Kubelka, Elzinandes Leal de Azeredo
Dengue is an acute febrile illness with a wide spectrum of signs and symptoms ranging from mild to severe forms characterized by plasma leakage that can be fatal. NK cells are one of the main effectors in early infection and may play an important role in dengue pathogenesis. We investigated NK cell involvement during dengue infection. A higher frequency of NK cell subsets and TRAIL+NK cells was found in mild DF cases when compared to that in severe cases or healthy donors. NK activation markers such as CD107a and TLR3 were upregulated in patients' cells compared to those in healthy donors...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29032654/tyndallized-lactobacillus-plantarum-hy7712-restores-whole-body-%C3%AE-irradiation-impaired-th-cell-differentiation-in-mice
#6
Se-Eun Jang, Da-Bin Ko, Young-Tae Ahn, Jae-Hun Shim, Cha Soon Kim, Dong Hyun Kim
In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole body γ-irradiated mice. Oral administration of tHY7712 strongly recovered γ-irradiation-suppressed expression of helper T (Th) cell- and regulatory T (Treg) cell-related transcription factors and cytokines such as T-bet, Foxp3, IFN-γ, TNF-α, and IL-10 and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively...
October 14, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29032460/the-impact-of-kir-hla-genotype-on-hepatitis-b-virus-clearance-in-iranian-infected-individuals
#7
Alireza Shah-Hosseini, Mohammad Jafari, Asadollah Mohammadi, Roozbeh Sanaei, Seyed Moayed Alavian, Amin Doosti-Irani, Mehrnoush Nooradeh Keykavousi, Nader Tajik
Killer cell immunoglobulin like receptors (KIRs) have a principal role in regulating the effector functions of NK cells, particularly in viral infections. The major ligands for KIRs are human leukocyte antigen (HLA) class I molecules. The aim of this study is to investigate the possible association of KIR genes, their known HLA ligands and compound KIR-HLA genotypes with hepatitis B virus (HBV) infection. Our study group consisted of 202 Iranian HBV-infected patients (52 spontaneously recovered, 50 asymptomatic carriers, 50 chronic sufferers and 50with liver cirrhosis) and 100 ethnic-matched healthy control subjects...
October 14, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/29032340/quinic-acid-inhibits-vascular-inflammation-in-tnf-%C3%AE-stimulated-vascular-smooth-muscle-cells
#8
Seon-A Jang, Dae Won Park, Jeong Eun Kwon, Hae Seong Song, Bongkyun Park, Hyelin Jeon, Eun-Hwa Sohn, Hyun Jung Koo, Se Chan Kang
Atherosclerosis is a chronic inflammatory disease, and the increased expression of adhesion molecules on vascular smooth muscle cells contributes to the progression of vascular disease. Quinic acid (QA) has been shown to possess radioprotection, anti-neuroinflammatory, and anti-oxidant activities; however, an anti-vascular inflammatory effect has not been reported. This study investigated the effect of QA on the expression of vascular cell adhesion molecule-1 (VCAM-1) stimulated by TNF-α in MOVAS cells. Pre-incubation of MOVAS cells, the mouse vascular smooth muscle cell line for 2h with QA (0...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29032017/editorial-next-generation-sequencing-technology-a-new-tool-for-killer-cell-immunoglobulin-like-receptor-allele-typing-in-hematopoietic-stem-cell-transplantation
#9
B Maniangou, C Retière, K Gagne
Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017)...
October 11, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#10
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#11
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29026144/increased-nk-cell-immunity-in-a-transgenic-mouse-model-of-nkp46-overexpression
#12
Ariella Glasner, Batya Isaacson, Sergey Viukov, Tzahi Neuman, Nehemya Friedman, Michal Mandelboim, Veronika Sexl, Jacob H Hanna, Ofer Mandelboim
Natural Killer (NK) cells employ activating receptors like the Natural Cytotoxicity Receptors (NCRs: NKp30, NKp44 and NKp46), of which only NKp46 has a mouse orthologue (Ncr1), to eliminate abnormal cells. NKp46/Ncr1 is considered a selective marker for NK cells, although it is also found on a subset of ILCs, where it appears to be without function. The influenza virus hemagglutinin (HA) was the first ligand identified for Ncr1/NKp46 followed by other viral, bacterial and even fungal ligands. NKp46/Ncr1 also recognizes unknown self and tumor ligands...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025767/monocytes-and-granulocytes-reduce-cd38-expression-levels-on-myeloma-cells-in-patients-treated-with-daratumumab
#13
Jakub Krejcik, Kristine A Frerichs, Inger S Nijhof, Berris van Kessel, Jeroen van Velzen, Andries C Bloem, Marloes Broekmans, Sonja Zweegman, Johan van Meerloo, René J Musters, Pino Poddighe, Richard Groen, Christopher Chiu, Torben Plesner, Henk M Lokhorst, A Kate Sasser, Tuna Mutis, Niels W C J van de Donk
PURPOSE: Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma (MM) cells. The aim of this study was to investigate the clinical implications and the underlying mechanisms of daratumumab-mediated CD38 reduction. EXPERIMENTAL DESIGN: We evaluated the effect of daratumumab alone or in combination with lenalidomide-dexamethasone, on CD38 levels of MM cells and non-tumor immune cells in the GEN501 study (daratumumab monotherapy) and the GEN503 study (daratumumab combined with lenalidomide-dexamethasone)...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29023581/activating-and-inhibitory-receptors-on-natural-killer-cells-in-patients-with-systemic-lupus-erythematosis-regulation-with-interleukin-15
#14
Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Ji-Yih Chen, Jing-Long Huang
Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score≥6), 26 age-matched healthy adults were used as controls...
2017: PloS One
https://www.readbyqxmd.com/read/29023417/control-of-nk-cell-activation-by-immune-checkpoint-molecules
#15
REVIEW
Asma Beldi-Ferchiou, Sophie Caillat-Zucman
The development of cancer and chronic infections is facilitated by many subversion mechanisms, among which enhanced expression of immune checkpoints molecules, such as programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), on exhausted T cells. Recently, immune checkpoint inhibitors have shown remarkable efficiency in the treatment of a number of cancers. However, expression of immune checkpoints on natural killer (NK) cells and its functional consequences on NK cell effector functions are much less explored...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29023371/expression-profiles-of-ligands-for-activating-natural-killer-cell-receptors-on-hiv-infected-and-uninfected-cd4%C3%A2-%C2%BA-t-cells
#16
Alexandra Tremblay-McLean, Julie Bruneau, Bertrand Lebouché, Irene Lisovsky, Rujun Song, Nicole F Bernard
Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4(-)) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV...
October 12, 2017: Viruses
https://www.readbyqxmd.com/read/29020784/-screening-of-endometrial-nk-cells-in-selected-infertile-patients-first-part-methods-and-current-results
#17
Z Ulčová-Gallová, M Pešek, P Chaloupka, P Mukešnábl, M Haschová, P Losan, K Bibková, Z Mičanová, J Cibulka
INTRODUCTION: Generaly, natural killer cells (NK cells) are among the most important cells of our immune defense system. They are present in the blood, decidua but also in secretory endometrium. OBJECTIVE: We investigate an association between high density of NK cells CD56+ and NK cells CD16+ into blood and secretory endometrium in patients with up to now unexplained recurrent miscarriage. At the same time, we focused on diagnosis of antiphospholipid syndrome, congenital trombophilic factors, stress factor, and lenght of hormonal contraception before conception...
2017: Ceská Gynekologie
https://www.readbyqxmd.com/read/29018442/lower-expression-of-microrna-155-contributes-to-dysfunction-of-natural-killer-cells-in-patients-with-chronic-hepatitis-b
#18
Jun Ge, Zuxiong Huang, Hongyan Liu, Jiehua Chen, Zhanglian Xie, Zide Chen, Jie Peng, Jian Sun, Jinlin Hou, Xiaoyong Zhang
MicroRNAs have been reported to be regulated in different ways in a variety of liver diseases. As a key modulator of cellular function in both innate and adaptive immunity, the role of miR-155 in chronic hepatitis B virus infection remains largely unknown. Here, we investigated the expression and function of miR-155 in chronic hepatitis B (CHB) patients. It was found that miR-155 expression in peripheral blood mononuclear cells (PBMCs) was lower in CHB patients than healthy controls (HC). Among CHB infection, immune-active (IA) patients with abnormal alanine aminotransferase (ALT) levels had relatively higher miR-155 expression in PBMCs and serum than immune-tolerant carriers, but were comparable to inactive carriers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018171/dual-enhancement-of-t-and-nk-cell-function-by-pulsatile-inhibition-of-ship1-improves-antitumor-immunity-and-survival
#19
Matthew Gumbleton, Raki Sudan, Sandra Fernandes, Robert W Engelman, Christopher M Russo, John D Chisholm, William G Kerr
The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells. However, unexpectedly, genetic ablation studies have shown that the effector functions of SHIP1-deficient NK and T cells are compromised in vivo...
October 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28994179/lysosome-targeting-amplifiers-of-reactive-oxygen-species-as-anticancer-prodrugs
#20
Andriy Mokhir, Steffen Daum, Viktor Reshetnikov, Miroslav Sisa, Tetyana Dymych, Maxim D Lootski, Rostyslav Bilyy, Evgenia Bila, Christina Janko, Christoph Alexiou, Martin Herrmann, Leopold Sellner
Cancer cells produce elevated amounts of reactive oxygen species that has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, where a prodrug reacts with ROS. However, at low µM concentrations of the prodrugs and ROS the activation is usually inefficient. Herein we suggested and validated a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted to its lysosome specific analogue...
October 9, 2017: Angewandte Chemie
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