Volume 1.06 | Apr 23

Human Immunology News 1.06 April 23, 2013
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Deficiency of β-Arrestin1 Ameliorates Collagen-Induced Arthritis with Impaired TH17 Cell Differentiation
Researchers showed that in patients with rheumatoid arthritis (RA), the expression of a multifunctional regulator β-arrestin1 was significantly up-regulated in peripheral and synovial CD4+ T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of β-arrestin1 ameliorated disease with decreased TH17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. [Proc Natl Acad Sci USA] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

Association between Specific Adipose Tissue CD4+ T-Cell Populations and Insulin Resistance in Obese People
The authors investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese, metabolically normal insulin-sensitive obese, and lean subjects. [Gastroenterology] Abstract

Therapeutical Potential of a Peptide Mimicking the SOCS1 Kinase Inhibitory Region in Skin Immune Responses
Investigators found that IFN-γ-activated keratinocytes treated with PS-5 exhibited impaired JAK2, IFN-γRa, and STAT1 phosphorylation. They also observed reduced levels of the IRF-1 transcription factor, and a strong reduction in ICAM-1, HLA-DR, CXCL10 and CCL2 inflammatory gene expression. ICAM-1 reduced expression resulted in an impaired adhesiveness of T lymphocytes to autologous keratinocytes. [Eur J Immunol] Abstract

Upregulation of OX40 Ligand on Monocytes Contributes to Early Virological Control in Patients with Chronic Hepatitis C
Dysfunctional HCV-specific CD4+ T cells are known to contribute to inadequate adaptive immunity in chronic hepatitis C (CHC), although the underlying mechanisms remain largely undefined. In this study, OX40 ligand expression was investigated in 41 treatment-naïve CHC patients, 20 sustained virological responders and 36 healthy subjects. [Eur J Immunol] Abstract

Long-Term Survival after Adoptive Bone Marrow T Cell Therapy of Advanced Metastasized Breast Cancer: Follow-Up Analysis of a Clinical Pilot Trial
Researchers recently described the immunologic effects of adoptive transfer of ex vivo restimulated tumor-reactive memory T cells (TCs) from the bone marrow of 12 metastasized breast cancer patients in a clinical phase-I study. In this trial, adoptive T cell transfer resulted in the occurrence of circulating tumor antigen-reactive type-1 TCs. They describe the long-term clinical outcome and its correlation with tumor-specific cellular immune response in 16 metastasized breast cancer patients, including 12 included in the original study. [Cancer Immunol Immunother] Abstract

The Hedgehog Inhibitor Cyclopamine Impairs the Benefits of Immunotherapy with Activated T and NK Lymphocytes Derived from Patients with Advanced Cancer
Scientists evaluated the effects of hedgehog (Hh) inhibition and oxygen concentrations on the function of activated T and NK (TNK) lymphocytes derived from patients with advanced cancer. Proliferation, migration, surface NKG2D expression, and cytotoxicity were all significantly inhibited, and IFN-γ secretion was significantly increased upon Hh inhibitor treatment of activated TNK lymphocytes under hypoxic conditions in vitro. [Cancer Immunol Immunother] Abstract

Anti-Inflammatory/Regulatory Cytokine Microenvironment Mediated by IL-4 and IL-10 Coordinates the Immune Response in Hemophilia A Patients Infected Chronically with Hepatitis C Virus
Focusing on the role of the immune system for controlling and or maintaining  hepatitis C virus (HCV) infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. [J Med Virol] Abstract

Pathogenic CCR6+ Dendritic Cells in the Skin Lesions of Discoid Lupus Patients: A Role for Damage-Associated Molecular Patterns
Researchers found an increase in conventional dendritic cells (cDCs) with inflammatory characteristics in the skin of discoid lupus erythematosus (DLE) patients, compared with control skins. Interestingly, cDCs from the DLE patients expressed low levels of the inhibitory molecule PD-L1 and showed a high expression of CCR6, which correlated with disease activity. [Eur J Dermatol] Abstract

MicroRNA Expressions in PMBCs, CD4+, and CD8+ T-Cells from Patients Suffering from Autoimmune Addison’s Disease
The authors aimed to determine key immunoregulatory microRNAs (miRNAs) influencing autoimmune adrenal insufficiency. For this purpose, selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD8+ cells of six patients with autoimmune adrenal insufficiency and ten healthy controls. [Horm Metab Res] Abstract

Maturation of Toll-Like Receptor 1-4 Responsiveness during Early Life
In order to achieve a more complete understanding of the ontogeny of immune system during the first years of life, researchers investigated age-matched toll-like receptor 1-4 responsiveness at several time points up to the age of two years. Mononuclear cells were isolated from cord blood and peripheral blood from infants at 6, 12, and 24 months of age, and from 50 adults. [Early Hum Dev]

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Progress in Immune-Based Therapies for Type 1 Diabetes
Type 1 diabetes is increasing in incidence, is peaking in ever-younger age groups, carries significant risk of increased morbidity and early mortality, and remains difficult to manage effectively in many settings. With these issues in mind, the authors review progress towards immune-based strategies for this chronic autoimmune disease. [Clin Exp Immunol] Abstract

NK Cell-Based Immunotherapy for Malignant Diseases
Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced. [Cell Mol Immunol] Abstract

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Mount Sinai Launches Phase III Clinical Trial of Novel, Personalized Vaccine for Newly-Diagnosed Kidney Cancer
Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma is a randomized, open-label multicenter clinical trial investigating the potential for AGS-003 plus standard targeted drug therapy to extend overall survival versus standard therapy alone. [The Icahn School of Medicine at Mount Sinai] Press Release

Novel Cancer Immunotherapy Set to Enter Clinical Trials
PDS Biotechnology Corporation presented a summary of the company’s preclinical data on its lead cancer immunotherapy PDS0101 at the World Vaccine Congress in Washington DC. The product is based on the company’s ground-breaking and proprietary Versamune™ nanotechnology vaccine platform. PDS Biotechnology also announced that the company’s Investigational New Drug application had been granted by the FDA allowing PDS0101 to be evaluated in human patients. [PR Newswire Association LLC] Press Release

2013 Rangos Award Winners
Meet the finalists for the 2013 Rangos Award for Creativity in Cancer Discovery and learn more about their new and innovative approaches to metastatic cancer research and treatment. [Johns Hopkins Medicine] Press Release

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National Institutes of Health (United States)

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NEW Allergy and Asthma 2013
May 23-24, 2013
Bruges, Belgium

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Scientist – Immunology (Crucell Holland B.V.)

Physician/Scientist – Tumor Immunotherapy (Stanford University School of Medicine)

Postdoctoral Fellow – Cancer Immunology (Dana-Farber Cancer Institute / Harvard Medical School)

Senior Director – Department of Immunology (Genentech, Inc.)

PhD Studentship (University of Lübeck, ISEF)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

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