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https://www.readbyqxmd.com/read/29785126/impact-of-targeting-transforming-growth-factor-%C3%AE-2-with-antisense-ot-101-on-the-cytokine-and-chemokine-profile-in-patients-with-advanced-pancreatic-cancer
#1
Osmond J D'Cruz, Sanjive Qazi, Larn Hwang, Kevin Ng, Vuong Trieu
Background: Overexpression of the cytokine - transforming growth factor-beta 2 (TGF-β2) - has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-β2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-β receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29776986/the-characteristics-of-vessel-lining-cells-in-normal-spleens-and-their-role-in-the-pathobiology-of-myelofibrosis
#2
Jiajing Qiu, Mohamed E Salama, Cing Siang Hu, Yan Li, Xiaoli Wang, Ronald Hoffman
The CD34- CD8α+ , sinusoid lining, littoral cells (LCs), and CD34+ CD8α- , splenic vascular endothelial cells (SVECs) represent 2 distinct cellular types that line the vessels within normal spleens and those of patients with myelofibrosis (MF). To further understand the respective roles of LCs and SVECs, each was purified from normal and MF spleens, cultured, and characterized. Gene expression profiling indicated that LCs were a specialized type of SVEC. LCs possessed a distinct gene expression profile associated with cytoskeleton regulation, cellular interactions, endocytosis, and iron transport...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29773448/the-role-of-the-common-gamma-chain-family-cytokines-in-%C3%AE-%C3%AE-t-cell-based-anti-cancer-immunotherapy
#3
REVIEW
Heleen H Van Acker, Diana Campillo-Davo, Gils Roex, Maarten Versteven, Evelien L Smits, Viggo F Van Tendeloo
Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anti-cancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (γδ) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade...
May 14, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29770360/biomarkers-associated-with-death-after-initiating-treatment-for-tuberculosis-and-hiv-in-patients-with-very-low-cd-4-cells
#4
Fred R Sattler, Daniel Chelliah, Xingye Wu, Alejandro Sanchez, Michelle A Kendall, Evelyn Hogg, David Lagat, Umesh Lalloo, Valdilea Veloso, Diane V Havlir, Alan Landay
Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3 ...
2018: Pathogens & Immunity
https://www.readbyqxmd.com/read/29769573/discovery-of-a-novel-il-15-based-protein-with-improved-developability-and-efficacy-for-cancer-immunotherapy
#5
Qiyue Hu, Xin Ye, Xiangdong Qu, Dongbing Cui, Lei Zhang, Zhibin Xu, Hong Wan, Lianshan Zhang, Weikang Tao
Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+ /CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769439/csf1r-dependent-myeloid-cells-are-required-for-nk%C3%A2-mediated-control-of-metastasis
#6
Michal Beffinger, Paulino Tallón de Lara, Sònia Tugues, Marijne Vermeer, Yannick Montagnolo, Isabel Ohs, Virginia Cecconi, Giulia Lucchiari, Aron Gagliardi, Nikola Misljencevic, James Sutton, Roman Spörri, Burkhard Becher, Anurag Gupta, Maries van den Broek
Myeloid leukocytes are essentially involved in both tumor progression and control. We show that neo-adjuvant treatment of mice with an inhibitor of CSF1 receptor (CSF1R), a drug that is used to deplete tumor-associated macrophages, unexpectedly promoted metastasis. CSF1R blockade indirectly diminished the number of NK cells due to a paucity of myeloid cells that provide the survival factor IL-15 to NK cells. Reduction of the number of NK cells resulted in increased seeding of metastatic tumor cells to the lungs but did not impact on progression of established metastases...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29754771/epstein-barr-virus-specific-cytokine-induced-killer-cells-for-treatment-of-epstein-barr-virus-related-malignant-lymphoma
#7
Lisa-Marie Pfeffermann, Verena Pfirrmann, Sabine Huenecke, Melanie Bremm, Halvard Bonig, Hans-Michael Kvasnicka, Thomas Klingebiel, Peter Bader, Eva Rettinger
BACKGROUND: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context. METHODS: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool...
May 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29754714/membrane-potential-distinctly-modulates-mobility-and-signaling-of-il-2-and-15-receptors-in-t-cells
#8
Éva Nagy, Gábor Mocsár, Veronika Sebestyén, Julianna Volkó, Ferenc Papp, Katalin Tóth, Sándor Damjanovich, György Panyi, Thomas A Waldmann, Andrea Bodnár, György Vámosi
The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K+ release from necrotic cells and hypoxia affecting the expression of K+ channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function...
May 10, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29738852/altered-maternal-immune-networks-are-associated-with-adverse-child-neurodevelopment-impact-of-alcohol-consumption-during-pregnancy
#9
Tamara S Bodnar, Charlis Raineki, Wladimir Wertelecki, Lyubov Yevtushok, Larisa Plotka, Natalya Zymak-Zakutnya, Gordon Honerkamp-Smith, Alan Wells, Matthieu Rolland, Todd S Woodward, Claire D Coles, Julie A Kable, Christina D Chambers, Joanne Weinberg
Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay...
May 5, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29737931/rux-largely-restores-lungs-in-iraq-pm-exposed-mice-up-regulating-regulatory-t-cells-tregs
#10
David Lin, Jonathan Li, Rabail Razi, Niha Qamar, Laurie Levine, Thomas Zimmerman, Sayyed A Hamidi, Millicent Schmidt, Marc G Golightly, Todd Rueb, Andrea Harrington, Merrill Garnett, Frank Antonawich, Steven McClain, Courtney Cox, Po Hsuan Huang, Anthony M Szema
Background Military personnel post-deployment to Iraq and Afghanistan have noted new-onset respiratory illness. This study's primary objective was to further develop an animal model of Iraq Afghanistan War Lung Injury (IAW-LI) and to test a novel class of anti-injury drug called RuX. Methods Particulate Matter (PM) samples were obtained in Iraq then characterized by spectromicroscopy. C57BL/6 mice underwent orotracheal instillation with PM, followed by drinkable treatment with RuX. Lung histology, inspiratory capacity (FlexiVent), thymic/splenic regulatory T cell (Treg) number, and whole-lung genomics were analyzed...
May 8, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29737525/cytomegalovirus-an-unlikely-ally-in-the-fight-against-blood-cancers
#11
Austin B Bigley, Forrest L Baker, Richard J Simpson
CMV infection is a potentially fatal complication in patients receiving HSCT, but recent evidence indicates that CMV has strong anti-leukemia effects due in part to shifts in the composition of NK-cell subsets. NK-cells are the primary mediators of the anti-leukemia effect of allogeneic HSCT and infusion of allogeneic NK-cells has shown promise as a means of inducing remission and preventing relapse of several different hematologic malignancies. The effectiveness of these treatments is limited, however, when tumors express HLA-E, a ligand for the inhibitory receptor NKG2A which is expressed by the vast majority of post-transplant reconstituted and ex vivo expanded NK-cells...
May 8, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29737430/hil-15-gene-modified-human-natural-killer-cells-nkl-il15-exhibit-anti-human-leukemia-functions
#12
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/29731959/identification-of-neoepitopes-recognized-by-tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#13
Davide Valentini, Martin Rao, Qingda Meng, Anna von Landenberg, Jiri Bartek, Georges Sinclair, Georgia Paraschoudi, Elke Jäger, Inti Harvey-Peredo, Ernest Dodoo, Markus Maeurer
Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of 'private' somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29728511/identification-of-cellular-sources-of-il-2-needed-for-regulatory-t-cell-development-and-homeostasis
#14
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/29721386/in-situ-delivery-of-allogeneic-natural-killer-cell-nk-combined-with-cetuximab-in-liver-metastases-of-gastrointestinal-carcinoma-a-phase-i-clinical-trial
#15
O Adotevi, Y Godet, J Galaine, Z Lakkis, I Idirene, J M Certoux, M Jary, R Loyon, C Laheurte, S Kim, A Dormoy, F Pouthier, C Barisien, F Fein, P Tiberghien, X Pivot, S Valmary-Degano, C Ferrand, P Morel, E Delabrousse, C Borg
Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29713323/implication-of-interleukin-12-15-18-and-ruxolitinib-in-the-phenotype-proliferation-and-polyfunctionality-of-human-cytokine-preactivated-natural-killer-cells
#16
Iñigo Terrén, Idoia Mikelez, Irati Odriozola, Andrea Gredilla, Javier González, Ane Orrantia, Joana Vitallé, Olatz Zenarruzabeitia, Francisco Borrego
A brief in vitro stimulation of natural killer (NK) cells with interleukin (IL)-12, IL-15, and IL-18 endow them a memory-like behavior, characterized by higher effector responses when they are restimulated after a resting period of time. These preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have several properties that make them a promising tool in cancer immunotherapy. In the present study, we have described the effect that different combinations of IL-12, IL-15, and IL-18 have on the generation of human CIML NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29699793/serum-interleukin-15-levels-in-patients-with-seropositive-myasthenia-gravis-do-not-correlate-with-disease-severity
#17
Ewa Sobieszczuk, Justyna Kubiszewska, Marta Lipowska, Piotr Szczudlik, Beata Szyluk, Małgorzata Dutkiewicz, Anna Kostera-Pruszczyk
AIM: To assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. BACKGROUND: IL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. PATIENTS AND METHODS: Sera of 42 seropositive MG patients (66...
January 6, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29695173/conditioned-media-from-human-osteoarthritic-synovium-induces-inflammation-in-a-synoviocyte-cell-line
#18
Elisa Belluzzi, Eleonora Olivotto, Giovanna Toso, Augusto Cigolotti, Assunta Pozzuoli, Carlo Biz, Giovanni Trisolino, Pietro Ruggieri, Brunella Grigolo, Roberta Ramonda, Marta Favero
AIM: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. MATERIALS AND METHODS: Conditioned media (CM) from cartilage, synovial membrane, meniscus and IFP, were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM)...
April 26, 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29693324/circulating-cytokine-profiles-and-anca-specificity-in-patients-with-anca-associated-vasculitis
#19
Alvise Berti, Roscoe Warner, Kent Johnson, Divi Cornec, Darrell Schroeder, Brian Kabat, Carol A Langford, Gary S Hoffman, Fernanado C Fervenza, Cees G M Kallenberg, Philip Seo, Robert Spiera, E William St Clair, Paul Brunetta, John H Stone, Peter A Merkel, Ulrich Specks, Paul A Monach
OBJECTIVES: To evaluate circulating cytokine profiles in patients with ANCA-associated vasculitis (AAV), classified by ANCA specificity (proteinase 3 (PR3)-ANCA versus myeloperoxidase (MPO)-ANCA) or by clinical diagnosis (granulomatosis with polyangiitis (GPA) versus microscopic polyangiitis (MPA)). METHODS: A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV (RAVE) trial. Cytokine concentrations were compared between groups within each classification system...
April 25, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29692776/interleukin-15-cultured-dendritic-cells-enhance-anti-tumor-gamma-delta-t-cell-functions-through-il-15-secretion
#20
Heleen H Van Acker, Sébastien Anguille, Hans De Reu, Zwi N Berneman, Evelien L Smits, Viggo F Van Tendeloo
Dendritic cell (DC) vaccination can be an effective post-remission therapy for acute myeloid leukemia (AML). Yet, current DC vaccines do not encompass the ideal stimulatory triggers for innate gamma delta (γδ) T cell anti-tumor activity. Promoting type 1 cytotoxic γδ T cells in patients with AML is, however, most interesting, considering these unconventional T cells are primed for rapid function and exert meaningful control over AML. In this work, we demonstrate that interleukin (IL)-15 DCs have the capacity to enhance the anti-tumoral functions of γδ T cells...
2018: Frontiers in Immunology
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