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https://www.readbyqxmd.com/read/30517864/cmv-primes-functional-alternative-signaling-in-adaptive-%C3%AE-g-nk-cells-but-is-subverted-by-lentivirus-infection-in-rhesus-macaques
#1
Spandan V Shah, Cordelia Manickam, Daniel R Ram, Kyle Kroll, Hannah Itell, Sallie R Permar, Dan H Barouch, Nichole R Klatt, R Keith Reeves
Despite burgeoning evidence demonstrating the adaptive properties of natural killer (NK) cells, mechanistic data explaining these phenomena are lacking. Following antibody sensitization, NK cells lacking the Fc receptor (FcR) signaling chain (Δg) acquire adaptive features, including robust proliferation, multifunctionality, rapid killing, and mobilization to sites of virus exposure. Using the rhesus macaque model, we demonstrate the systemic distribution of Δg NK cells expressing memory features, including downregulated Helios and Eomes...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30514793/-cd16-nkg2ahigh-natural-killer-cells-infiltrate-breast-cancer-draining-lymph-nodes
#2
Alexandra Frazao, Meriem Messaoudene, Nicolas Núñez, Nicolas Dulphy, France Roussin, Christine Sedlik, Laurence Zitvogel, Eliane Piaggio, Antoine Toubert, Anne Caignard
Tumor-draining lymph nodes (TD-LNs) are the first site of metastasis of breast cancer (BC). Natural killer (NK) cells that infiltrate TD-LNs (including non-invaded (NI) or metastatic (M)-LNs from BC patients) and NK cells from healthy donor (HD)-LN were characterized, and their phenotype analyzed by flow cytometry. Low percentages of tumor cells invaded M-LNs, and these cells expressed ULBP2 and HLA class I molecules. Although NK cells from paired NI and M-LNs were similar, they expressed different markers compared to HD-LN NK cells...
December 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/30514403/purinergic-targeting-enhances-immunotherapy-of-cd73-solid-tumors-with-piggybac-engineered-chimeric-antigen-receptor-natural-killer-cells
#3
Jiao Wang, Kyle B Lupo, Andrea M Chambers, Sandro Matosevic
BACKGROUND: The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo...
December 4, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30514329/mutated-von-hippel-lindau-renal-cell-carcinoma-rcc-promotes-patients-specific-natural-killer-nk-cytotoxicity
#4
Anna Maria Trotta, Sara Santagata, Serena Zanotta, Crescenzo D'Alterio, Maria Napolitano, Giuseppina Rea, Rosa Camerlingo, Fabio Esposito, Elvira Lamantia, Annamaria Anniciello, Giovanni Botti, Nicola Longo, Gerardo Botti, Sandro Pignata, Sisto Perdonà, Stefania Scala
BACKGROUND: Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function. METHODS: VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-γ production...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30513816/targeting-adenosine-receptor-signaling-in-cancer-immunotherapy
#5
REVIEW
Kevin Sek, Christina Mølck, Gregory D Stewart, Lev Kats, Phillip K Darcy, Paul A Beavis
The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of 'checkpoint blockade' and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient's own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function...
December 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30512185/b7h6-is-a-functional-ligand-for-nkp30-in-rat-and-cattle-and-determines-nkp30-reactivity-towards-human-cancer-cell-lines
#6
Elisabeth G Bjørnsen, Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Camilla Henden, Per C Saether, Preben Boysen, Michael R Daws, Erik Dissen
NK cells kill cancer cells and infected cells upon activation by cell surface receptors. Human NKp30 is an activating receptor expressed by all mature NK cells. The B7 family member B7H6 has been identified as one ligand for NKp30. Several alternative ligands have also been reported, and the field remains unsettled. To this end, we have identified full-length functional B7H6 orthologs in rat and cattle, demonstrated by phylogenetic analysis and transfection experiments. In cell-cell contact-dependent assays, chimeric NKp30 reporter cells responded strongly to B7H6 in rat and cattle...
December 4, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/30510994/dipeptidyl-peptidase-4-inhibitors-reduce-hepatocellular-carcinoma-by-activating-lymphocyte-chemotaxis-in-mice
#7
Sohji Nishina, Akira Yamauchi, Takumi Kawaguchi, Kohei Kaku, Moritaka Goto, Kyo Sasaki, Yuichi Hara, Yasuyuki Tomiyama, Futoshi Kuribayashi, Takuji Torimura, Keisuke Hino
Background & Aims: CD26, a multifunctional transmembrane glycoprotein, is expressed in various cancers and functions as dipeptidyl peptidase 4 (DPP4). We investigated whether CD26 expression is associated with hepatocellular carcinoma (HCC) progression and whether DPP4 inhibitors exert antitumor effects against HCC. Methods: CD26 expression was examined in 41 surgically resected HCC specimens. The effects of DPP4 inhibitors on HCC were examined by using HCC cell lines (Huh-7 and Li-7), xenograft tumors in nude mice, and a nonalcoholic steatohepatitis-related HCC mouse model...
2019: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30508863/acute-exercise-increases-the-expression-of-kir2ds4-by-promoter-demethylation-in-nk-cells
#8
Alexander Schenk, Walter Pulverer, Christine Koliamitra, Claus Juergen Bauer, Suzana Ilic, Rudolf Heer, Robert Schier, Volker Schick, Bernd W Böttiger, Clarissa Gerhäuser, Wilhelm Bloch, Philipp Zimmer
Positive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50-60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention...
December 3, 2018: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/30504141/cd226-regulates-natural-killer-cell-antitumor-responses-via-phosphorylation-mediated-inactivation-of-transcription-factor-foxo1
#9
Xiangnan Du, Patricia de Almeida, Nick Manieri, Denise de Almeida Nagata, Thomas D Wu, Kristin Harden Bowles, Vidhyalakshmi Arumugam, Jill Schartner, Rafael Cubas, Stephanie Mittman, Vincent Javinal, Keith R Anderson, Søren Warming, Jane L Grogan, Eugene Y Chiang
Natural killer (NK) cell recognition of tumor cells is mediated through activating receptors such as CD226, with suppression of effector functions often controlled by negative regulatory transcription factors such as FOXO1. Here we show that CD226 regulation of NK cell cytotoxicity is facilitated through inactivation of FOXO1. Gene-expression analysis of NK cells isolated from syngeneic tumors grown in wild-type or CD226-deficient mice revealed dysregulated expression of FOXO1-regulated genes in the absence of CD226...
November 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30503213/anti-nkg2a-mab-is-a-checkpoint-inhibitor-that-promotes-anti-tumor-immunity-by-unleashing-both-t-and-nk-cells
#10
Pascale André, Caroline Denis, Caroline Soulas, Clarisse Bourbon-Caillet, Julie Lopez, Thomas Arnoux, Mathieu Bléry, Cécile Bonnafous, Laurent Gauthier, Ariane Morel, Benjamin Rossi, Romain Remark, Violette Breso, Elodie Bonnet, Guillaume Habif, Sophie Guia, Ana Ines Lalanne, Caroline Hoffmann, Olivier Lantz, Jérôme Fayette, Agnès Boyer-Chammard, Robert Zerbib, Pierre Dodion, Hormas Ghadially, Maria Jure-Kunkel, Yannis Morel, Ronald Herbst, Emilie Narni-Mancinelli, Roger B Cohen, Eric Vivier
Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells...
November 13, 2018: Cell
https://www.readbyqxmd.com/read/30503208/nkg2a-blockade-potentiates-cd8-t-cell-immunity-induced-by-cancer-vaccines
#11
Nadine van Montfoort, Linda Borst, Michael J Korrer, Marjolein Sluijter, Koen A Marijt, Saskia J Santegoets, Vanessa J van Ham, Ilina Ehsan, Pornpimol Charoentong, Pascale André, Nicolai Wagtmann, Marij J P Welters, Young J Kim, Sytse J Piersma, Sjoerd H van der Burg, Thorbald van Hall
Tumor-infiltrating CD8 T cells were found to frequently express the inhibitory receptor NKG2A, particularly in immune-reactive environments and after therapeutic cancer vaccination. High-dimensional cluster analysis demonstrated that NKG2A marks a unique immune effector subset preferentially co-expressing the tissue-resident CD103 molecule, but not immune checkpoint inhibitors. To examine whether NKG2A represented an adaptive resistance mechanism to cancer vaccination, we blocked the receptor with an antibody and knocked out its ligand Qa-1b , the conserved ortholog of HLA-E, in four mouse tumor models...
November 7, 2018: Cell
https://www.readbyqxmd.com/read/30500089/natural-selection-for-killer-receptors-and-their-mhc-class-i-ligands-in-pursuit-of-gene-pairs-that-fit-well-in-tandem
#12
REVIEW
Michael G Brown, Awndre Gamache, William T Nash, John Cronk
Our understanding of the genetic basis of host resistance to viral infection and disease has progressed significantly over the last century. Numerous genes coding for modifiers of immune functions have been identified, which impact a variety of critical cellular processes, including signaling via lymphocyte receptors and their ligands, signal transduction, cytokine signaling, production and release of cytotoxic effectors, transcriptional regulation, and proliferation. Genome-wide association studies implicate an important role for both highly polymorphic NK cell receptors and their MHC class I ligands in modifying host resistance...
November 30, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/30498897/safety-and-efficacy-of-targeted-alpha-therapy-with-213-bi-dota-substance-p-in-recurrent-glioblastoma
#13
Leszek Królicki, Frank Bruchertseifer, Jolanta Kunikowska, Henryk Koziara, Bartosz Królicki, Maciej Jakuciński, Dariusz Pawlak, Christos Apostolidis, Saed Mirzadeh, Rafał Rola, Adrian Merlo, Alfred Morgenstern
Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter 213 Bi allows for selective irradiation and killing of tumor cells. MATERIAL AND METHODS: Twenty patients with recurrent GBM were included into the study following a standard therapy...
November 29, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/30498034/genetic-determinants-and-an-epistasis-of-lilra3-and-hla-b-52-in-takayasu-arteritis
#14
Chikashi Terao, Hajime Yoshifuji, Takayoshi Matsumura, Taeko K Naruse, Tomonori Ishii, Yoshikazu Nakaoka, Yohei Kirino, Keitaro Matsuo, Tomoki Origuchi, Masakazu Shimizu, Yasuhiro Maejima, Eisuke Amiya, Natsuko Tamura, Takahisa Kawaguchi, Meiko Takahashi, Kazuya Setoh, Koichiro Ohmura, Ryu Watanabe, Tetsuya Horita, Tatsuya Atsumi, Mitsuru Matsukura, Tetsuro Miyata, Yuta Kochi, Toshio Suda, Kazuo Tanemoto, Akira Meguro, Yukinori Okada, Akiyoshi Ogimoto, Motohisa Yamamoto, Hiroki Takahashi, Shingo Nakayamada, Kazuyoshi Saito, Masataka Kuwana, Nobuhisa Mizuki, Yasuharu Tabara, Atsuhisa Ueda, Issei Komuro, Akinori Kimura, Mitsuaki Isobe, Tsuneyo Mimori, Fumihiko Matsuda
Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted...
November 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30497469/tendinosis-like-changes-in-denervated-rat-achilles-tendon
#15
Roine El-Habta, Jialin Chen, Jessica Pingel, Ludvig J Backman
BACKGROUND: Tendon disorders are common and lead to significant disability and pain. Our knowledge of the 'tennis elbow', the 'jumpers knee', and Achilles tendinosis has increased over the years, but changes in denervated tendons is yet to be described in detail. The aim of the present study was to investigate the morphological and biochemical changes in tendon tissue following two weeks of denervation using a unilateral sciatic nerve transection model in rat Achilles tendons. METHODS: Tendons were compared with respect to cell number, nuclear roundness, and fiber structure...
November 30, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/30488123/acute-epstein-barr-virus-positive-cytotoxic-t-cell-lymphoid-hyperplasia-in-the-upper-aerodigestive-tract-mimicking-extranodal-natural-killer-t-cell-lymphoma-nasal-type
#16
Xie Jianlan, Huang Yuhua, Zheng Yuanyuan, Zhang Yanlin, Wei Ping, Liu Wei, Zhou Xiaoge, Jin Mulan
To describe the clinicopathological features of nine patients with acute Epstein-Barr virus (EBV)-positive cytotoxic T cell lymphoid hyperplasia (EBV+TLH) in the upper aerodigestive tract, in which initial findings led to a preliminary misdiagnosis of extranodal NK/T cell lymphoma, nasal type (ENKTL). A series of nine cases of EBV+TLH in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 16 years (range 5-29 years) with a M:F ratio of 5:4. All patients were previously healthy with an acute onset period of < 1 month...
November 28, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/30487792/effect-of-age-on-nk-cell-compartment-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#17
Paulo Rodrigues-Santos, Nelson López-Sejas, Jani Sofia Almeida, Lenka Ruzičková, Patricia Couceiro, Vera Alves, Carmen Campos, Corona Alonso, Raquel Tarazona, Paulo Freitas-Tavares, Rafael Solana, Manuel Santos-Rosa
Natural killer (NK) cells are a very important component of the innate immune response involved in the lysis of virus infected and tumor cells. Aging has a profound impact in the frequency, phenotype and function of NK cells. Chronic Myeloid Leukemia (CML) is caused by the BCR-ABL gene formation encoding aberrant oncoprotein tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) induces durable deep molecular response. The response to treatment and life expectancy is lower in older patients with chronic phase of CML than in younger patients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30487278/identification-and-functional-characterization-of-a-novel-fc-gamma-binding-glycoprotein-in-rhesus-cytomegalovirus
#18
Philipp Kolb, Steven Sijmons, Matthew R McArdle, Husam Taher, Jennie Womack, Colette Hughes, Abigail Ventura, Michael A Jarvis, Christiane Stahl-Hennig, Scott Hansen, Louis J Picker, Daniel Malouli, Hartmut Hengel, Klaus Früh
Receptors recognizing the Fc part of immunoglobulin G (FcγRs) are key determinants in antibody-mediated immune responses. Members of the Herpesviridae interfere with this immune regulatory network by expressing viral FcγRs (vFcγRs). Human cytomegalovirus (HCMV) encodes four distinct vFcγRs that differ with respect to their IgG-subtype specificity and their impact on antibody-mediated immune function in vitro The impact of vFcγRs on HCMV pathogenesis and immunomodulation in vivo is not known. The evolutionary closest animal model of HCMV is rhesus CMV (RhCMV) infection of rhesus macaques...
November 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30487267/fine-needle-aspirates-comprehensively-sample-intrahepatic-immunity
#19
Upkar S Gill, Laura J Pallett, Niclas Thomas, Alice R Burton, Amit A Patel, Simon Yona, Patrick T F Kennedy, Mala K Maini
OBJECTIVE: In order to refine new therapeutic strategies in the pipeline for HBV cure, evaluation of virological and immunological changes compartmentalised at the site of infection will be required. We therefore investigated if liver fine needle aspirates (FNAs) could comprehensively sample the local immune landscape in parallel with viable hepatocytes. DESIGN: Matched blood, liver biopsy and FNAs from 28 patients with HBV and 15 without viral infection were analysed using 16-colour multiparameter flow cytometry...
November 28, 2018: Gut
https://www.readbyqxmd.com/read/30486888/immunotherapy-utilizing-the-combination-of-natural-killer-and-antibody-dependent-cellular-cytotoxicity-adcc-mediating-agents-with-poly-adp-ribose-polymerase-parp-inhibition
#20
Kathleen E Fenerty, Michelle Padget, Benjamin Wolfson, Sofia R Gameiro, Zhen Su, John H Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong, James W Hodge
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent single-stranded DNA repair. Olaparib is a PARPi approved for the treatment of BRCA mutant ovarian and breast carcinoma. Emerging clinical data suggest a benefit of combining olaparib with immunotherapy in prostate cancer patients both with and without somatic BRCA mutations. METHODS: We examined if olaparib, when combined with IgG1 antibody-dependent cellular cytotoxicity (ADCC)-mediating monoclonal antibodies (mAbs) cetuximab (anti-EGFR), or avelumab (anti-PD-L1), would increase tumor cell sensitivity to killing by natural killer (NK) cells independently of BRCA status or mAb target upregulation...
November 29, 2018: Journal for Immunotherapy of Cancer
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