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Amy K Erbe, Wei Wang, Jacob Goldberg, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, James W Mier, David J Panka, David F McDermott, Paul M Sondel
BACKGROUND: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated anti-tumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of cancer patients treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines...
October 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Ziye Pan, Jinjiao He, Lubna M Rasoul, Yunye Liu, Ruixiang Che, Yun Ding, Xiaocheng Guo, Jiarui Yang, Dehua Zou, Hua Zhang, Deshan Li, Hongwei Cao
Recombinant Newcastle disease virus (rNDV) is tumor selective and intrinsically oncolytic, which has been developed as a vector to express exogenous genes to enhance its oncolytic efficacy. Our previous studies found that insertion sites of foreign gene in rNDV vector affected its expression and anti-tumor activities. However, the optimal insertion site for foreign genes remains unknown. In this study, we inserted the enhanced green fluorescence protein (EGFP) and IL2 genes into four different intergenic regions of the rNDV using reverse genetics technology...
2016: PloS One
Giovanni Grandi, Lucrezia Pignatti, Francesca Ferrari, Giulia Dante, Isabella Neri, Fabio Facchinetti
INTRODUCTION: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis. Matherials and Methods: Singleton pregnancies between 24-30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment...
October 9, 2016: Journal of Maternal-fetal & Neonatal Medicine
Wei Wang, Amy K Erbe, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, Jonathan M Weiss, James Mier, David Panka, David F McDermott, Paul M Sondel
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition...
September 30, 2016: Cancer Immunology, Immunotherapy: CII
Tereza C Cardoso, Lucas H Okamura, Jamila C Baptistella, Roberto Gameiro, Helena L Ferreira, Márcia Marinho, Eduardo F Flores
The possibility of isolating bovine mesenchymal multipotent stromal cells (MSCs) from fetal adnexa is an interesting prospect due to the potential use of these cells in biotechnological applications. However, little is known about the properties of these progenitor cells in bovine species. Wharton's jelly (WJ) MSC cells were obtained from the umbilical cord of bovine fetuses at three different stages of pregnancy and divided into groups 1, 2 and 3 according to gestational trimester. Cell morphology, from the three stages of pregnancy, typically appeared fibroblast-like spindle-shaped, presenting the same viability and number...
September 27, 2016: Cell and Tissue Research
Andrew A Somogyi, Alex T Sia, Ene-Choo Tan, Janet K Coller, Mark R Hutchinson, Daniel T Barratt
Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously...
July 14, 2016: Pain
M Orciani, A Campanati, M Caffarini, G Ganzetti, V Consales, G Lucarini, A Offidani, R Di Primio
BACKGROUND: Atopic dermatitis (AD) is a chronic, and inflammatory disease characterized by a marked imbalance of Th2 versus Th1-Th17 in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by atopic dermatitis (AD). OBJECTIVE: the relative expression of 22 genes encoding for Th1, Th2, and Th17 cytokines and the secretion of the corresponding proteins have been analyzed in Cutaneous Mesenchymal Stem Cells (MSCs) isolated from skin of AD patients (AD-MSCs) to evaluate their role on AD onset...
September 17, 2016: British Journal of Dermatology
Shanieek Lawrence, Samuel T Pellom, Anil Shanker, Margaret M Whalen
Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo...
September 7, 2016: Journal of Immunotoxicology
Lukasz S Wylezinski, Jacek Hawiger
The pleiotropic cytokine interleukin 2 (IL2), disrupts the blood-brain barrier and alters brain microcirculation, underlying Vascular Leak Syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been previously determined. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex...
September 6, 2016: Journal of Biological Chemistry
P J Holmes, S C Peiper, G K Uppal, J Z Gong, Z-X Wang, R Bajaj
INTRODUCTION: Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013...
October 2016: International Journal of Laboratory Hematology
Usha Agrawal, Nitu Kumari, Ashwani K Mishra, Pawan Vasudeva, Anup Kumar, Nayan K Mohanty, Sunita Saxena
BACKGROUND: Urothelial carcinoma (UC) is one of most common genitourinary malignancy and the spectrum of disease ranges from in situ lesions to muscle-invasive cancers. The non-muscle-invasive lesions have tendency to recur or progress to muscle-invasive disease. The study of the immune profile may identify immune determinants associated with high-grade, recurrence, and invasion in patients with UC. METHODS: Pathway-focused RT(2) profiler arrays were used to screen patients with UC for dysregulation of candidate genes of Th1-Th2-Th3 and NFκB pathways, which were then validated by real-time polymerase chain reaction on tumor samples and correlated with grade, recurrence, and invasion of tumors to identify their role in predicting behavior of the tumor...
September 2016: Urologic Oncology
Shalini Vellasamy, Chih Kong Tong, Nur Atiqah Azhar, Radha Kodiappan, Soon Choy Chan, Abhi Veerakumarasivam, Rajesh Ramasamy
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated. METHODS: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord-derived MSCs (UC-MSCs) on activated T cells...
October 2016: Cytotherapy
Bo Guan, Fengxiang Chen, Shuai Su, Zuoying Duan, Yun Chen, Huazhong Li, Jian Jin
Pichia pastoris is generally considered as an expression host for heterologous proteins with the coding gene under control of the alcohol oxidase 1 (AOX1) promoter. The secretion of heterologous proteins in P. pastoris can be potentially affected by many factors. Based on our previous results, the secretion levels of human albumin (HSA) fusion protein IL2-HSA were only around 500 mg/L or less in fermentor cultures, which decreased more than 50% comparing to that of HSA (>1 g/L). In this study, we selected five potential secretion helper factors, in which Ero1, Pdi1 and Kar2 involved in protein folding and Sec1 and Sly1 involved in vesicle trafficking...
August 17, 2016: Yeast
Clarissa Silva Martins, Daniel Elias, Leandro Machado Colli, Carlos Eduardo Couri, Manoel Carlos L A Souza, Ayrton C Moreira, Milton C Foss, Lucila L K Elias, Margaret de Castro
CONTEXT: Metabolic syndrome (MetS) shares several similarities with hypercortisolism. OBJECTIVES: To evaluate hypothalamic-pituitary-adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls. DESIGN: Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirao Preto Medical School University Hospital...
August 9, 2016: Diabetes/metabolism Research and Reviews
Andrew L Doedens, Mark P Rubinstein, Emilie T Gross, J Adam Best, David H Craig, Megan K Baker, David J Cole, Jack D Bui, Ananda W Goldrath
Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration...
September 2, 2016: Cancer Immunology Research
Antonio Pinto, Annika Jahn, Moritz Benjamin Immohr, Alexander Jenke, Laura Döhrn, Markus Kornfeld, Artur Lichtenberg, Payam Akhyari, Udo Boeken
Everolimus (EVL) is widely used in solid organ transplantation. It is known to have antiproliferative and immunosuppressive abilities via inhibition of the mTOR pathway. Preventive EVL administration may lower inflammation induced by cardiopulmonary bypass (CPB) and reduce systemic inflammatory response syndrome (SIRS). After oral loading with EVL 2.5 mg/kg/day (n = 11) or placebo (n = 11) for seven consecutive days, male Wistar rats (400-500 g) were connected to a miniaturised heart-lung-machine performing a deep hypothermic circulatory arrest protocol...
October 2016: Inflammation
Zachary D Hudson, Brian J Miller
INTRODUCTION: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We performed a metaanalysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews. METHODS: We identified articles by systematic searches of Pub Med, PsycInfo, and ISI, and the reference lists of identified studies...
July 25, 2016: Clinical Schizophrenia & related Psychoses
Said Farschtschi, Su-Jin Park, Birgit Sawitzki, Su-Jun Oh, Lan Kluwe, Victor F Mautner, Andreas Kurtz
Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations...
September 2016: Cancer Immunology, Immunotherapy: CII
Mkunde Chachage, Georgios Pollakis, Edmund Osei Kuffour, Kerstin Haase, Asli Bauer, Yuka Nadai, Lilli Podola, Petra Clowes, Matthias Schiemann, Lynette Henkel, Dieter Hoffmann, Sarah Joseph, Sabin Bhuju, Leonard Maboko, Fred Stephen Sarfo, Kirsten Eberhardt, Michael Hoelscher, Torsten Feldt, Elmar Saathoff, Christof Geldmacher
UNLABELLED: Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers...
October 15, 2016: Journal of Virology
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