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https://www.readbyqxmd.com/read/27919749/in-vitro-vla-4-blockade-results-in-an-impaired-nk-cell-mediated-immune-surveillance-against-melanoma
#1
Ilaria Gandoglia, Federico Ivaldi, Paolo Carrega, Eric Armentani, Guido Ferlazzo, Gianluigi Mancardi, Nicole Kerlero de Rosbo, Antonio Uccelli, Alice Laroni
Natalizumab (NTZ) is a monoclonal antibody targeting the α4β1 integrin (CD49d/CD29), very late antigen-4 (VLA-4), which is approved for treatment of relapsing-remitting multiple sclerosis (RR-MS). A possible association between NTZ treatment and a higher risk of melanoma is under debate. Natural Killer (NK) cells, which express VLA-4, represent an innate barrier limiting spreading of melanoma under steady state conditions. Indeed, because of their expression of activating receptors, they are very efficient in recognizing and killing melanoma cells without the need of a previous priming...
December 2, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#2
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27899617/epigenetic-and-genetic-deregulation-in-cancer-target-distinct-signaling-pathway-domains
#3
Yang Gao, Andrew E Teschendorff
Cancer is characterized by both genetic and epigenetic alterations. While cancer driver mutations and copy-number alterations have been studied at a systems-level, relatively little is known about the systems-level patterns exhibited by their epigenetic counterparts. Here we perform a pan-cancer wide systems-level analysis, mapping candidate cancer-driver DNA methylation (DNAm) alterations onto a human interactome. We demonstrate that functional DNAm alterations in cancer tend to map to nodes of lower connectivity and inter-connectivity, compared to the corresponding alterations at the genomic level...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27884732/natural-killer-cell-subsets-and-receptor-expression-in-peripheral-blood-mononuclear-cells-of-a-healthy-korean-population-reference-range-influence-of-age-and-sex-and-correlation-between-nk-cell-receptors-and-cytotoxicity
#4
Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, Duck Cho
BACKGROUND: The purpose of this study was to identify CD56(bright) and CD56(dim) natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3(-)/CD56(dim) and CD3(-)/CD56(bright) NK cells in whole-blood samples from 122 healthy donors...
November 21, 2016: Human Immunology
https://www.readbyqxmd.com/read/27871469/placental-telomere-length-decline-with-gestational-age-differs-by-sex-and-tert-dnmt1-and-dnmt3a-dna-methylation
#5
Samantha L Wilson, Yao Liu, Wendy P Robinson
INTRODUCTION: Telomere length (TL) has been suggested to be influenced by inherited genetic and epigenetic variation, hormonal effects, oxidative stress and age. However, the dynamics of TL during in utero development have not been well explored. This study investigates the relationship between placental TL and sex, gestational age (GA), and DNA methylation (DNAm). Placental TL is further evaluated in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR), conditions hypothesized to lead to decreased placental TL due to increased oxidative stress...
December 2016: Placenta
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#6
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27785870/senescence-associated-dna-methylation-is-stochastically-acquired-in-subpopulations-of-mesenchymal-stem-cells
#7
Julia Franzen, Anne Zirkel, Jonathon Blake, Björn Rath, Vladimir Benes, Argyris Papantonis, Wolfgang Wagner
Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types...
October 26, 2016: Aging Cell
https://www.readbyqxmd.com/read/27783105/high-efficiency-lysis-of-cervical-cancer-by-allogeneic-nk-cells-derived-from-umbilical-cord-progenitors-is-independent-of-hla-status
#8
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
October 25, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27777574/phenotypic-and-functional-dysregulated-blood-nk-cells-in-colorectal-cancer-patients-can-be-activated-by-cetuximab-plus-il-2%C3%A2-or-il-15
#9
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27757317/highly-efficient-il-21-and-feeder-cell-driven-ex-vivo-expansion-of-human-nk-cells-with-therapeutic-activity-in-a-xenograft-mouse-model-of-melanoma
#10
Markus Granzin, Ana Stojanovic, Matthias Miller, Richard Childs, Volker Huppert, Adelheid Cerwenka
Natural killer (NK) cells are promising antitumor effector cells, but the generation of sufficient NK cell numbers for adoptive immunotherapy remains challenging. Therefore, we developed a method for highly efficient ex vivo expansion of human NK cells. Ex vivo expansion of NK cells in medium containing IL-2 and irradiated clinical-grade feeder cells (EBV-LCL) induced a 22-fold NK cell expansion after one week that was significantly increased to 53-fold by IL-21. Repeated stimulation with irradiated EBV-LCL and IL-2 and addition of IL-21 at the initiation of the culture allowed sustained NK cell proliferation with 10(11)-fold NK cell expansion after 6 weeks...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27756784/tgf%C3%AE-r1-blockade-with-galunisertib-ly2157299-enhances-anti-neuroblastoma-activity-of-anti-gd2-antibody-dinutuximab-ch14-18-with-natural-killer-cells
#11
Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim, Shahab Asgharzadeh, Robert C Seeger
PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL DESIGN: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis...
October 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27733551/distinct-roles-for-human-cytomegalovirus-immediate-early-proteins-ie1-and-ie2-in-the-transcriptional-regulation-of-mica-and-pvr-cd155-expression
#12
Benedetta Pignoloni, Cinzia Fionda, Valentina Dell'Oste, Anna Luganini, Marco Cippitelli, Alessandra Zingoni, Santo Landolfo, Giorgio Gribaudo, Angela Santoni, Cristina Cerboni
Elimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I-related chain (MIC) A/B and UL16-binding proteins (ULBP)1-6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell-mediated lysis of infected cells...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27723147/can-a-six-letter-alphabet-increase-the-likelihood-of-photochemical-assault-to-the-genetic-code
#13
Brennan Ashwood, Marvin Pollum, Carlos E Crespo-Hernández
In 2014, two unnatural nucleosides, d5SICS and dNaM, were shown to selectively base pair and replicate with high fidelity in a modified strain of E. coli, thus effectively expanding its genetic alphabet from four to six letters. More recently, a significant reduction in cell proliferation was reported in cells cultured with d5SICS, and putatively with dNaM, upon exposure to brief periods of near-visible radiation. The photosensitizing properties of the lowest-energy excited triplet state of both d5SICS and dNaM were implicated in their cytotoxicity...
October 10, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27697858/il-2-variant-circumvents-icos-regulatory-t-cell-expansion-and-promotes-nk-cell-activation
#14
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27690265/dna-methylation-based-measures-of-biological-age-meta-analysis-predicting-time-to-death
#15
Brian H Chen, Riccardo E Marioni, Elena Colicino, Marjolein J Peters, Cavin K Ward-Caviness, Pei-Chien Tsai, Nicholas S Roetker, Allan C Just, Ellen W Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L Lunetta, Joanne M Murabito, Stefania Bandinelli, Dena G Hernandez, David Melzer, Michael Nalls, Luke C Pilling, Timothy R Price, Andrew B Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M Visscher, Sonia Shah, Naomi R Wray, Allan F McRae, Oscar H Franco, Albert Hofman, André G Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E Levine, Ake T Lu, Philip S Tsao, Lifang Hou, JoAnn E Manson, Cara L Carty, Andrea Z LaCroix, Alexander P Reiner, Tim D Spector, Andrew P Feinberg, Daniel Levy, Andrea Baccarelli, Joyce van Meurs, Jordana T Bell, Annette Peters, Ian J Deary, James S Pankow, Luigi Ferrucci, Steve Horvath
Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality...
September 28, 2016: Aging
https://www.readbyqxmd.com/read/27687885/characterizing-the-hypomethylated-dna-methylation-profile-of-nucleated-red-blood-cells-from-cord-blood
#16
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
AIM: To provide insight into fetal nucleated red blood cell (nRBC) development using genome-wide DNA methylation (DNAm) profiling. MATERIALS & METHODS: The DNAm profile (Illumina 450K array) of cord blood (n = 7) derived nRBCs was compared with B cells, CD4 and CD8 T cells, natural killer cells, granulocytes, monocytes and placenta (n = 5). RESULTS: nRBCs and placenta had similarly low array-wide DNAm compared with white blood cells, but their patterns of hypomethylation differed at biologically relevant subsets of the array...
September 30, 2016: Epigenomics
https://www.readbyqxmd.com/read/27646016/a-systematic-review-of-dna-methylation-and-preterm-birth-in-african-american-women
#17
Veronica Barcelona de Mendoza, Michelle L Wright, Comfort Agaba, Laura Prescott, Alexandra Desir, Cindy A Crusto, Yan V Sun, Jacquelyn Y Taylor
BACKGROUND: The causes of many cases of preterm birth (PTB) remain enigmatic. Increased understanding of how epigenetic factors are associated with health outcomes has resulted in studies examining DNA methylation (DNAm) as a contributing factor to PTB. However, few studies on PTB and DNAm have included African American women, the group with the highest rate of PTB. METHODS: The objective of this review was to systematically analyze the existing studies on DNAm and PTB among African American women...
September 19, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27634931/the-lncrna-hotair-impacts-on-mesenchymal-stem-cells-via-triple-helix-formation
#18
Marie Kalwa, Sonja Hänzelmann, Sabrina Otto, Chao-Chung Kuo, Julia Franzen, Sylvia Joussen, Eduardo Fernandez-Rebollo, Björn Rath, Carmen Koch, Andrea Hofmann, Shih-Han Lee, Andrew E Teschendorff, Bernd Denecke, Qiong Lin, Martin Widschwendter, Elmar Weinhold, Ivan G Costa, Wolfgang Wagner
There is a growing perception that long non-coding RNAs (lncRNAs) modulate cellular function. In this study, we analyzed the role of the lncRNA HOTAIR in mesenchymal stem cells (MSCs) with particular focus on senescence-associated changes in gene expression and DNA-methylation (DNAm). HOTAIR binding sites were enriched at genomic regions that become hypermethylated with increasing cell culture passage. Overexpression and knockdown of HOTAIR inhibited or stimulated adipogenic differentiation of MSCs, respectively...
September 14, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27623136/beneficial-in-vitro-effects-of-interleukin-2-interleukin-12-and-their-combination-on-functional-and-receptor-characteristics-of-natural-killer-cells-in-metastatic-melanoma-patients-with-normal-serum-lactate-dehydrogenase-levels
#19
Katarina M Mirjačić Martinović, Nada Lj Babović, Radan R Džodić, Vladimir B Jurišić, Aleksandra Z Ninković, Gordana M Konjević
Considering tumor-mediated suppression of natural killer (NK) cells, the aim of this study was to investigate the in-vitro effects of interleukin (IL)-2 and IL-12, as immunostimulatory cytokines, on the functional and receptor characteristics of NK cells and their subsets in healthy control (HC) and metastatic melanoma (MM) patients. Peripheral blood mononuclear cells of 27 HC and 35 MM patients were stimulated in vitro with IL-2, IL-12, and their combination for functional and phenotypic analysis. IL-2, IL-12, and primarily their combination, significantly induced NK cell activity, CD107a degranulation marker, and perforin expression in NK cells and their subsets in HC and MM patients...
September 10, 2016: Melanoma Research
https://www.readbyqxmd.com/read/27622064/loss-of-dnam-1-ligand-expression-by-acute-myeloid-leukemia-cells-renders-them-resistant-to-nk-cell-killing
#20
Conor J Kearney, Kelly M Ramsbottom, Ilia Voskoboinik, Phillip K Darcy, Jane Oliaro
Acute myeloid leukemia (AML) is associated with poor natural killer (NK) cell function through aberrant expression of NK-cell-activating receptors and their ligands on tumor cells. These alterations are thought to promote formation of inhibitory NK-target cell synapses, in which killer cell degranulation is attenuated. Allogeneic stem cell transplantation can be effective in treating AML, through restoration of NK cell lytic activity. Similarly, agents that augment NK-cell-activating signals within the immunological synapse may provide some therapeutic benefit...
August 2016: Oncoimmunology
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