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https://www.readbyqxmd.com/read/29683892/implication-of-highly-cytotoxic-natural-killer-cells-for-esophageal-squamous-cell-carcinoma-treatment
#1
Kee Siang Lim, Kosaku Mimura, Ley-Fang Kua, Kensuke Shiraishi, Koji Kono
Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29683419/haemagglutinin-neuraminidase-from-hpiv3-mediates-human-nk-regulation-of-t-cell-proliferation-via-nkp44-and-nkp46
#2
Samantha McQuaid, Sinead Loughran, Patrick Power, Paula Maguire, Dermot Walls, Maria Grazia Cusi, Claes Orvell, Patricia Johnson
HPIV3 is a respiratory virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. Currently there is no effective vaccine or anti-viral therapy for this virus. Studies have suggested that poor T cell proliferation following HPIV3 infection is responsible for impaired immunological memory associated with this virus. We have previously demonstrated that NK cells mediate regulation of T cell proliferation during HPIV3 infection. Here we add to these studies by demonstrating that the regulation of T cell proliferation during HPIV3 infection is mediated via NK receptors NKp44 and NKp46 and involves the surface glycoprotein haemagglutinin-neuraminidase but not the fusion protein of the virus...
April 23, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29682537/the-potential-virulence-factors-of-providencia-stuartii-motility-adherence-and-invasion
#3
Naziia Kurmasheva, Vyacheslav Vorobiev, Margarita Sharipova, Tatyana Efremova, Ayslu Mardanova
Providencia stuartii is the most common Providencia species capable of causing human infections. Currently P. stuartii is involved in high incidence of urinary tract infections in catheterized patients. The ability of bacteria to swarm on semisolid (viscous) surfaces and adhere to and invade host cells determines the specificity of the disease pathogenesis and its therapy. In the present study we demonstrated morphological changes of P. stuartii NK cells during migration on the viscous medium and discussed adhesive and invasive properties utilizing the HeLa-M cell line as a host model...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29682376/a-case-of-spontaneously-improving-secondary-hemophagocytic-lymphohistiocytosis-in-an-adult-associated-with-t-cell-histiocyte-rich-large-b-cell-lymphoma
#4
Cyrus Askin, Ashley Burris, Clifton Layman, Brian Haney, Jordan Hall
Secondary hemophagocytic lymphohistiocytosis (HLH) in adults is a rare, often fatal syndrome characterized by widespread immune dysregulation. It is seen as a complication of infections, autoimmune diseases, and malignancies. Among the malignancy-related causes, aggressive T-cell or NK-cell neoplasms are most notable, while B-cell lymphomas are less commonly implicated. We present the case of a 32-year-old male transferred to our facility with concern for HLH. During the first week of his hospitalization, his diagnosis was confirmed and the patient demonstrated spontaneous improvement in his symptoms prompting us to delay therapy while searching for a primary cause...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29681767/evaluation-of-lymphocyte-response-to-the-induced-oxidative-stress-in-a-cohort-of-ageing-subjects-including-semisupercentenarians-and-their-offspring
#5
Federico Sizzano, Sebastiano Collino, Ornella Cominetti, Daniela Monti, Paolo Garagnani, Rita Ostan, Chiara Pirazzini, Maria Giulia Bacalini, Daniela Mari, Giuseppe Passarino, Claudio Franceschi, Alessio Palini
The production of reactive oxygen species (ROS) may promote immunosenescence if not counterbalanced by the antioxidant systems. Cell membranes, proteins, and nucleic acids become the target of ROS and progressively lose their structure and functions. This process could lead to an impairment of the immune response. However, little is known about the capability of the immune cells of elderly individuals to dynamically counteract the oxidative stress. Here, the response of the main lymphocyte subsets to the induced oxidative stress in semisupercentenarians (CENT), their offspring (OFF), elderly controls (CTRL), and young individuals (YO) was analyzed using flow cytometry...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29681501/further-evidence-for-depletion-of-peripheral-blood-natural-killer-cells-in-patients-with-schizophrenia-a-computational-deconvolution-study
#6
Paweł Karpiński, Jerzy Samochowiec, Dorota Frydecka, Maria M Sąsiadek, Błażej Misiak
Dysregulation of innate and adaptive immunity is increasingly being recognized as one of core characteristics of schizophrenia pathophysiology. Several studies have revealed that patients with schizophrenia present various alterations in the levels of distinct leukocyte subpopulations. However, studies addressing this point have provided mixed results. Therefore, in this study we translated a computational deconvolution algorithm in order to estimate counts of distinct leukocyte subpopulations in peripheral blood of patients with schizophrenia...
April 19, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29680663/loss-of-ovarian-function-in-association-with-a-high-fat-diet-promotes-insulin-resistance-and-disturbs-adipose-tissue-immune-homeostasis
#7
Munkyong Pae, Yunjung Baek, Seungeun Lee, Dayong Wu
Loss of ovarian function, as occurs in menopause or after ovariectomy (OVX), is associated with insulin resistance. Adipose tissue inflammation is suggested to be a key component of obesity-induced insulin resistance in male rodents. However, little is known about the effect of OVX and diet on insulin resistance in association with immune homeostasis. Thus, we conducted this study to determine how high-fat diet (HFD) and OVX, alone or in combination, impacted adipose tissue inflammation and insulin resistance...
March 20, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29679656/pd-1-blocks-lytic-granule-polarization-with-concomitant-impairment-of-integrin-outside-in-signaling-in-natural-killer-cell-immunological-synapse
#8
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29679602/solubility-enhanced-gmyl6-fused-with-a-hexa-lysine-tag-promotes-the-cytotoxicity-of-human-nk-cells
#9
Juanjuan Liu, Yuanyuan Jin, Xiaozhou Feng, Sen Zou, Guangxin Lv, Zhifei Zhang, Zhaoyong Yang
Goat myosin light chain 6 (gMYL6) is a constituent of certain extracted immunization-induced goat anti-cancer bioactive peptides (ACBPs). However, little is known about its activity onto NK cells which are the basic cellular attackers in cancer immunotherapy for patients with malignancies. Because of the complicated extraction process and low yield of gMYL6 out of the goat ACBPs' mixture, the Nano-flow liquid chromatography and C-terminal polycationic tag expression strategy were used to identify and enrich the peptide to investigate its bioactivity against cancers/tumors...
April 18, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29679556/a-novel-smac-mimetic-apg-1387-exhibited-dual-antitumor-effect-on-hbv-positive-hepatocellular-carcinoma-with-high-expression-of-ciap2-by-inducing-apoptosis-and-enhancing-innate-anti-tumor-immunity
#10
Wentao Pan, Qiuyun Luo, Xianglei Yan, Luping Yuan, Hanjie Yi, Lin Zhang, Baoxia Li, Yuxin Zhang, Jian Sun, Miao-Zhen Qiu, Da-Jun Yang
Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, SMAC mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs)...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29679490/increased-nk-cell-subsets-with-inhibitory-cytokines-and-inhibitory-surface-receptors-in-patients-with-recurrent-miscarriage-and-decreased-or-normal-subsets-in-kidney-transplant-recipients-late-post-transplant
#11
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Naruemol Ekpoom, Gerhard Opelz, Volker Daniel
BACKGROUND: Patients with recurrent miscarriage (RM) show up-regulated cytotoxic NK cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). METHODS: NK, NKT and T cell subsets were analyzed in the peripheral blood of 31 RM, 14 female ESRD and 9 female TX patients as well as 21 female HC using eight-color fluorescence flow cytometry...
April 21, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29679487/allergen-specific-immunotherapy-induces-regulatory-t-cells-in-an-atopic-dermatitis-mouse-model
#12
Jung U Shin, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim, Kim Hye Ran, Kyoung Yong Jeong, Kyung Hee Park, Jungsoo Lee, Howard Chu, Jae-Hyun Lee, Tai-Soon Yong, Jung-Won Park, Kwang Hoon Lee
BACKGROUND: Several studies have demonstrated that allergen-specific immunotherapy (SIT) can be an effective treatment for atopic dermatitis (AD). However, there is no relevant mouse model to investigate the mechanism and validate the novel modality of SIT in AD. METHODS: NC/Nga mice with induced AD-like skin lesions received a subcutaneous injection of SIT (an extract of the house dust mite Dermatophagoides farinae [DfE]) or placebo for 5 weeks). Clinical and histological improvements of AD-like skin lesions were examined...
April 21, 2018: Allergy
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#13
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29678809/delayed-immune-reconstitution-after-allogeneic-transplantation-increases-the-risks-of-mortality-and-chronic-gvhd
#14
Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Aleksandr Lazaryan, Xianghua Luo, Julie Curtsinger, Rohtesh S Mehta, Erica Warlick, Sarah A Cooley, Bruce R Blazar, Jeffrey S Miller, Daniel Weisdorf, John E Wagner, Michael R Verneris
Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29676596/lung-dendritic-cells-drive-nk-cytotoxicity-in-chronic-obstructive-pulmonary-disease-via-il-15r%C3%AE
#15
Donna K Finch, Valerie R Stolberg, John Ferguson, Henrih Alikaj, Mohamed R Kady, Bradley W Richmond, Vasiliy V Polosukhin, Timothy S Blackwell, Lisa McCloskey, Jeffrey L Curtis, Christine M Freeman
RATIONALE: Lung natural killer (NK) cells kill a greater percentage of autologous lung parenchymal cells in COPD than in non-obstructed smokers. To become cytotoxic, NKs require priming, typically by dendritic cells (DC), but whether priming occurs in the lungs in COPD is unknown. METHODS: We used lung tissue and in some cases peripheral blood from patients undergoing clinically-indicated resections to determine in vitro killing of CD326+ lung epithelial cells by isolated lung CD56+ NKs...
April 20, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29676151/activation-of-human-natural-killer-cells-by-graphene-oxide-templated-antibody-nanoclusters
#16
Christian Loftus, Mezida Saeed, Daniel M Davis, Iain E Dunlop
An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins...
April 20, 2018: Nano Letters
https://www.readbyqxmd.com/read/29675689/natural-killer-cells-in-liver-diseases
#17
REVIEW
Meijuan Zheng, Haoyu Sun, Zhigang Tian
The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals...
April 19, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29674648/human-intraepithelial-lymphocytes
#18
REVIEW
Toufic Mayassi, Bana Jabri
The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+ CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+ CD8αα+ and adaptively induced TCRαβ+ CD8αβ+ IEL subsets, respectively...
April 20, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29674644/aggressive-natural-killer-cell-leukemia-mutational-landscape-and-drug-profiling-highlight-jak-stat-signaling-as-therapeutic-target
#19
Olli Dufva, Matti Kankainen, Tiina Kelkka, Nodoka Sekiguchi, Shady Adnan Awad, Samuli Eldfors, Bhagwan Yadav, Heikki Kuusanmäki, Disha Malani, Emma I Andersson, Paavo Pietarinen, Leena Saikko, Panu E Kovanen, Teija Ojala, Dean A Lee, Thomas P Loughran, Hideyuki Nakazawa, Junji Suzumiya, Ritsuro Suzuki, Young Hyeh Ko, Won Seog Kim, Shih-Sung Chuang, Tero Aittokallio, Wing C Chan, Koichi Ohshima, Fumihiro Ishida, Satu Mustjoki
Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29674449/induction-of-antitumor-cytotoxic-lymphocytes-using-engineered-human-primary-blood-dendritic-cells
#20
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
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