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https://www.readbyqxmd.com/read/29737430/hil-15-gene-modified-human-natural-killer-cells-nkl-il15-exhibit-anti-human-leukemia-functions
#1
Wen Jiang, Cai Zhang, Zhigang Tian, Jian Zhang
PURPOSE: Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo...
May 8, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29728511/identification-of-cellular-sources-of-il-2-needed-for-regulatory-t-cell-development-and-homeostasis
#2
David L Owen, Shawn A Mahmud, Kieng B Vang, Ryan M Kelly, Bruce R Blazar, Kendall A Smith, Michael A Farrar
The cytokine IL-2 is critical for promoting the development, homeostasis, and function of regulatory T (Treg) cells. The cellular sources of IL-2 that promote these processes remain unclear. T cells, B cells, and dendritic cells (DCs) are known to make IL-2 in peripheral tissues. We found that T cells and DCs in the thymus also make IL-2. To identify cellular sources of IL-2 in Treg cell development and homeostasis, we used Il2FL/FL mice to selectively delete Il2 in T cells, B cells, and DCs. Because IL-15 can partially substitute for IL-2 in Treg cell development, we carried out the majority of these studies on an Il15-/- background...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29709683/a-single-preovulatory-administration-of-ulipristal-acetate-affects-the-decidualization-process-of-the-human-endometrium-during-the-receptive-period-of-the-menstrual-cycle
#3
Saúl Lira-Albarrán, Marta Durand, David Barrera, Claudia Vega, Rocio García Becerra, Lorenza Díaz, Janice García-Quiroz, Claudia Rangel, Fernando Larrea
In order to get further information on the effects of ulipristal acetate (UPA) upon the process of decidualization of endometrium, a functional analysis of the differentially expressed genes in endometrium (DEG) from UPA treated-versus control-cycles of normal ovulatory women was performed. A list of 1183 endometrial DEG, from a previously published study by our group, was submitted to gene ontology, gene enrichment and ingenuity pathway analyses (IPA). This functional analysis showed that decidualization was a biological process overrepresented...
April 27, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29696308/role-of-mda5-and-interferon-i-in-dendritic-cells-for-t-cell-expansion-by-anti-tumor-peptide-vaccines-in-mice
#4
Hussein Sultan, Juan Wu, Takumi Kumai, Andres M Salazar, Esteban Celis
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion...
April 25, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il-15-trans-presentation
#5
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29626271/bursal-immunopathology-responses-of-specific-pathogen-free-chickens-and-red-jungle-fowl-infected-with-very-virulent-infectious-bursal-disease-virus
#6
Mohd Isa Farhanah, Abdul Rahaman Yasmin, Nguyen Phuc Khanh, Swee Keong Yeap, Mohd Hair-Bejo, Abdul Rahman Omar
Very virulent infectious bursal disease virus (vvIBDV) targets B lymphocytes in the bursa of Fabricius (BF), causing immunosuppression and increased mortality rates in young birds. There have been few studies on the host immune response following vvIBDV infection at different inoculum doses in chickens with different genetic backgrounds. In this study, we characterized the immune responses of specific-pathogen-free (SPF) chickens and Malaysian red jungle fowl following infection with vvIBDV strain UPM0081 at 103...
April 6, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29596991/a-novel-strategy-to-produce-high-level-and-high-purity-of-bioactive-il15-fusion-proteins-from-mammalian-cells
#7
Haomin Huang, Yuying Luo, Hanna Baradei, Shan Liu, Keneshia K Haenssen, Supriya Sanglikar, Senthil Kumar, John Cini
IL15, a member of the common γ chain receptor (γc) cytokine family, is gaining attention in recent years as one of the most promising anti-tumor agents. IL15 regulates T cell activation and proliferation, promotes the survival of CD8+ CD44hi memory T cells and is also essential for NK cell expansion and development. Despite the attraction of developing IL15 as an anti-cancer agent, production of recombinant IL15 has proven to be difficult due to the stringent control of IL15 expression at the transcriptional, translational and the post-translational levels...
March 26, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29528261/influence-of-il15-gene-variations-on-the-clinical-features-treatment-response-and-risk-of-developing-childhood-acute-lymphoblastic-leukemia-in-latvian-population
#8
Dmitrijs Rots, Madara Kreile, Sergejs Nikulshin, Zhanna Kovalova, Linda Gailite
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study...
February 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29525407/skeletal-muscle-o-glcnac-transferase-is-important-for-muscle-energy-homeostasis-and-whole-body-insulin-sensitivity
#9
Hao Shi, Alexander Munk, Thomas S Nielsen, Morgan R Daughtry, Louise Larsson, Shize Li, Kasper F Høyer, Hannah W Geisler, Karolina Sulek, Rasmus Kjøbsted, Taylor Fisher, Marianne M Andersen, Zhengxing Shen, Ulrik K Hansen, Eric M England, Zhiyong Cheng, Kurt Højlund, Jørgen F P Wojtaszewski, Xiaoyong Yang, Matthew W Hulver, Richard F Helm, Jonas T Treebak, David E Gerrard
OBJECTIVE: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. METHODS: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry...
May 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29514797/cd16a-activation-of-nk-cells-promotes-nk-cell-proliferation-and-memory-like-cytotoxicity-against-cancer-cells
#10
Jens H W Pahl, Joachim Koch, Jana-Julia Götz, Annette Arnold, Uwe Reusch, Thorsten Gantke, Erich Rajkovic, Martin Treder, Adelheid Cerwenka
CD16A is a potent cytotoxicity receptor on human natural killer (NK) cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas...
May 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29504848/signalling-pathways-identified-in-salivary-glands-from-primary-sj%C3%A3-gren-s-syndrome-patients-reveal-enhanced-adipose-tissue-development
#11
Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
May 2018: Autoimmunity
https://www.readbyqxmd.com/read/29503743/-out-sourcing-for-trans-presentation-assessing-t-cell-intrinsic-and-extrinsic-il-15-expression-with-il15-gene-reporter-mice
#12
REVIEW
Joo-Young Park, Davinna L Ligons, Jung-Hyun Park
IL-15 is a cytokine of the common γ-chain family that is critical for natural killer (NK), invariant natural killer T ( i NKT), and CD8 memory T cell development and homeostasis. The role of IL-15 in regulating effector T cell subsets, however, remains incompletely understood. IL-15 is mostly expressed by stromal cells, myeloid cells, and dendritic cells (DCs). Whether T cells themselves can express IL-15, and if so, whether such T cell-derived IL-15 could play an autocrine role in T cells are interesting questions that were previously addressed but answered with mixed results...
February 2018: Immune Network
https://www.readbyqxmd.com/read/29477012/treg-and-nk-cells-related-cytokines-are-associated-with-deep-rectosigmoid-endometriosis-and-clinical-symptoms-related-to-the-disease
#13
Bárbara Yasmin Gueuvoghlanian-Silva, Patrick Bellelis, Denise Frediani Barbeiro, Camila Hernandes, Sergio Podgaec
The aim of this study was to evaluate Treg and NK cells related cytokines in deep infiltrating endometriosis lesions and its relationship with clinical symptoms of the disease. mRNA expression of Transforming Growth Factor Beta (TGFB), Interleukin (IL)10, Interferon Gamma (IFNG), IL7, and IL15 was analyzed by Real-Time PCR in eutopic endometrium and rectosigmoid lesions from 11 women with deep infiltrating endometriosis and in eutopic endometrium from 11 healthy women. IL10, IFNG, and IL7 expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from women with endometriosis...
April 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29462197/thymic-epithelial-cell-derived-signals-control-b-progenitor-formation-and-proliferation-in-the-thymus-by-regulating-let-7-and-arid3a
#14
Shiyun Xiao, Wen Zhang, Nancy R Manley
The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus and have been recently shown to impact T cell selection, however, the mechanisms controlling B cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice, down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week after birth caused a dramatic reduction of T progenitors and an increase of B cell progenitors. This time point is coincident with the switch from fetal to adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7 system...
2018: PloS One
https://www.readbyqxmd.com/read/29459477/intrinsic-functional-potential-of-nk-cell-subsets-constrains-retargeting-driven-by-chimeric-antigen-receptors
#15
Vincent Yi Sheng Oei, Marta Siernicka, Agnieszka Graczyk-Jarzynka, Hanna Julie Hoel, Weiwen Yang, Daniel Palacios, Hilde Almåsbak, Malgorzata Bajor, Dennis Clement, Ludwig Brandt, Björn Önfelt, Jodie Goodridge, Magdalena Winiarska, Radoslaw Zagozdzon, Johanna Olweus, Jon-Amund Kyte, Karl-Johan Malmberg
Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles...
April 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29448959/impaired-t-cell-mediated-hepatitis-in-peroxisome-proliferator-activated-receptor-alpha-ppar%C3%AE-deficient-mice
#16
Ian N Hines, Michael Kremer, Sherri M Moore, Michael D Wheeler
BACKGROUND: Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). METHODS: Wild type (wt) or PPARα-deficient (PPARα-/- ) mice were treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury, cytokine response, T cell activation and characterization...
February 15, 2018: Biological Research
https://www.readbyqxmd.com/read/29408034/insights-into-leghorn-male-hepatocellular-cells-response-to-fowl-adenovirus-serotype-4-infection-by-transcriptome-analysis
#17
Junqin Zhang, Zhong Zou, Kun Huang, Xian Lin, Huanchun Chen, Meilin Jin
Fowl adenovirus serotype 4 (FAdV-4), a member of the Aviadenovirus genus of the Adenoviridae family, causes hepatitis-hydropericardium syndrome (HHS) in chickens. It causes mortality of up to 80% in 3-6-week-old broilers, posing a substantial threat to the poultry industry. However, the specific host responses to the virus are not well understood. To better understand the interactions between the host and FAdV-4 and to explore the pathogenesis of this virus, a high-throughput RNA-seq technology was utilized with leghorn male hepatocellular (LMH) cells at 12, 24, and 48 h after FAdV-4 infection...
February 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-therapy-synergizes-with-anti-pd-1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#18
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veera Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by the tumor suppressor gene TUSC2 (also known as FUS1 ) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras -mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
February 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29308327/enhancement-of-antibody-dependent-cellular-cytotoxicity-of-cetuximab-by-a-chimeric-protein-encompassing-interleukin-15
#19
Maria Carmen Ochoa, Luna Minute, Ascensión López, Elisabeth Pérez-Ruiz, Celia Gomar, Marcos Vasquez, Susana Inoges, Iñaki Etxeberria, Inmaculada Rodriguez, Saray Garasa, Jan-Peter Andreas Mayer, Peter Wirtz, Ignacio Melero, Pedro Berraondo
Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8+ T cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29224228/newcastle-disease-virus-co-expressing-interleukin-7-and-interleukin-15-modified-tumor-cells-as-a-vaccine-for-cancer-immunotherapy
#20
Xiaojing Xu, Qing Sun, Yu Mei, Yonghao Liu, Lixiang Zhao
Interleukin 15 (IL15) and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) through incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro...
February 2018: Cancer Science
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