Volume 1.33 | Oct 29

Human Immunology News 1.33 October 29, 2013
Human Immunology News
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Major Cancer Regressions in Mesothelioma after Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression
Researchers describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of ten patients with chemotherapy-refractory mesothelioma, three have had major tumor regressions with two ongoing at 15 months, and two others responded to chemotherapy after discontinuing immunotoxin therapy. [Sci Transl Med] Abstract | Press Release
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PUBLICATIONS ( Ranked by impact factor of the journal)
The CYP27B1 Variant Associated with Increased Risk of Autoimmune Disease Is Underexpressed in Tolerising Dendritic Cells
Scientists showed that CYP27B1 is predominantly expressed in dendritic cells (DC). Its expression in these cells is necessary for their response to Vitamin D, which is known to upregulate pathways involved in generating a tolerogenic DC phenotype. [Hum Mol Genet] Abstract

Cytokine Responses of Peripheral Blood Mononuclear Cells to Allergen Do Not Identify Asthma or Asthma Phenotypes
Scientists investigated hypothesis that peripheral blood mononuclear cells from asthma patients with different phenotypes would react characteristically to a panel of common aeroallergens. [Clin Exp Allergy] Abstract

HLA-E Restricted CD8+ T Cell Subsets Are Phenotypically Altered in Multiple Sclerosis Patients
The importance of Qa-1 restricted CD8+ T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). The authors hypothesized that their human variant, HLA-E restricted CD8+ T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. [Mult Scler] Abstract

IL7Rα Expression and Upregulation by IFNβ in Dendritic Cell Subsets Is Haplotype-Dependent
Researchers showed that IL7R expression increases in myeloid cells in response to interferon beta (IFNβ), but that the response is haplotype-dependent, with cells from homozygotes for haplotype 4 showing no response. [PLoS One] Full Article

Decreased HPV-Specific T Cell Responses and Accumulation of Immunosuppressive Influences in Oropharyngeal Cancer Patients following Radical Therapy
Investigators aimed to determine the effect of radical therapy on human papillomavirus (HPV)-specific T cells and other immune parameters in 20 oropharyngeal cancer patients, as a prelude to future immunotherapy studies. [Cancer Immunol Immunother] Abstract

The Association among Leukocyte Apoptosis, Autoantibodies and Disease Severity in Systemic Lupus Erythematosus
The authors tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of systemic lupus erythematosus (SLE). Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D on each subtype of leukocyte in 23 patients with SLE. [J Transl Med] Full Article

CD4+CD25highFoxp3+ Regulatory T Lymphocytes Suppress IFNγ and CD107 Expression in CD4+ and CD8+ T Cells from Tuberculous Pleural Effusions
Scientists investigated the role of regulatory T cells in the modulation of Th1 responses in patients with tuberculous pleurisy. They demonstrated that the proportion of CD4+CD25+, CD4+CD25highFoxp3+ and CD8+CD25 + cells were increased in pleural fluid compared to peripheral blood samples. [Clin Exp Immunol] Abstract

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Inflammation-Induced Cancer: Crosstalk between Tumors, Immune Cells and Microorganisms
The authors outline the principal cellular and molecular pathways that coordinate the tumor-promoting and tumor-antagonizing effects of inflammation and they discuss the crosstalk between cancer development and inflammatory processes. [Nat Rev Cancer] Abstract

Age-Dependent Dysregulation of Innate Immunity
As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types and that vary depending on the cell activation state and tissue context. This aging-associated basal inflammation, particularly in humans, is thought to be induced by several factors, including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors. [Nat Rev Immunol] Abstract

IgA Deficiency and Autoimmunity
The mutations leading to IgA deficiency have not been defined, but in some cases of IgA deficiency it has been suggested that the pathogenesis involves a failure in switched memory B cells that can lead to this cohort experiencing an increased incidence of recurrent bacterial infections or autoimmune diseases. Attempts to investigate the role of cytokines that can induce IgA synthesis in cells of patients with IgA deficiency, such as IL21 or the combination of CD40L/anti-CD40, IL-4 and IL10, are underway. [Autoimmun Rev] Abstract

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Merck Announces Presentation of Interim Data from Phase IB Study of MK-3475, Investigational Anti-PD-1 Immunotherapy, in Previously-Treated Patients with Non-Small Cell Lung Cancer (NSCLC)
Merck announced the presentation of interim data from a Phase 1B trial evaluating MK-3475, an investigational anti-PD-1 immunotherapy, in patients with previously-treated NSCLC. [Press release from Merck discussing research presented at the 15th World Conference on Lung Cancer, Sydney] Press Release

Medication Used to Control Blood Sugar in People with Type 2 Diabetes May Also Reduce the Risk of Autoimmune Diseases
Researchers studied how often people with type 2 diabetes taking a dipeptidyl peptidase-4 inhibitor developed autoimmune diseases – such as rheumatoid arthritis, lupus, inflammatory bowel disease, psoriasis and multiple sclerosis – when compared to those not taking one. [Press release from Newswise, Inc. discussing research presented at the American College of Rheumatology Annual Meeting, San Diego] Press Release

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Immunicum Doses the First Patient in a New Clinical Phase I/II-Study in Primary Liver Cancer
The first patient in Immunicum’s clinical Phase I/II-study in primary liver cancer received the initial dose of the therapeutic cancer vaccine INTUVAX®. The liver cancer study will include a total of 12 patients and is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The primary objective is to investigate whether INTUVAX® is safe, but immunological response and overall survival will also be evaluated. [Immunicum AB] Press Release

Advaxis Appoints Gregory T. Mayes as Chief Operating Officer
Advaxis, Inc., a leader in developing the next generation of immunotherapies for cancer and infectious diseases, announced that it has appointed Gregory T. Mayes to the new position of Executive Vice President and Chief Operating Officer. [Advaxis, Inc.] Press Release
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Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 2014 Clinical Immunology Society (CIS) Annual Meeting: Primary Immune Deficiency Diseases North American Conference
April 10-13, 2014
Baltimore, United States

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NEW Postdoctoral Fellowship – Characterizing the Immunosuppressive Impact of Mesenchymal Stem Cells on T Cells (FDA: Center for Biologics Evaluation and Research)

Postdoctoral Research Position – Immunology (Singapore Immunology Network [SIgN])

Research Fellow – Cellular Immunity in Type 1 Diabetes (King’s College London)

Postdoctoral Fellow – Immunotherapy (Washington University School of Medicine)

PhD Fellowship – Chronic Vagus Nerve Stimulation as Therapy for Colitis (KU Leuven)

Postdoctoral Position – Autoimmunity (University of Chicago)

PhD Research Position – Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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