Volume 3.31 | Aug 11

Human Immunology News 3.31 August 11, 2015
Human Immunology News
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Genome-Wide Analysis of the Genetic Regulation of Gene Expression in Human Neutrophils
Investigators report an eQTL study on isolated neutrophils from 114 healthy individuals of Chinese ethnicity, identifying 21,210 eQTLs on 832 unique genes. Unsupervised clustering analysis of these eQTLs confirms their role in inflammatory responses and immunological diseases but also indicates strong involvement in dermatological pathologies. [Nat Commun] Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
CBP30, a Selective CBP/p300 Bromodomain Inhibitor, Suppresses Human Th17 Responses
The authors report data to support selective bromodomain blockade of the transcriptional coactivators CBP (CREB binding protein) and p300 as an alternative approach to inhibit human Th17 responses. In unbiased cellular testing on a diverse panel of cultured primary human cells, CBP30 reduced immune cell production of IL-17A and other proinflammatory cytokines. [Proc Natl Acad Sci USA] Abstract | Full Article

TIGIT+ Circulating Follicular Helper T Cells Display Robust B Cell Help Functions: Potential Role in Sickle Cell Alloimmunization
Investigators showed that a previously unidentified subset of human circulating T follicular helper cells expressing TIGIT, the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains, exhibit strong B cell help functions. [Haematologica] Abstract | Full Article

Human IL-21+IFN-γ+CD4+ T Cells in Nasal Polyps Are Regulated by IL-12
Scientists report that CD4+ T cells were the major IL-21-expressing cells in nasal polyp (NP) tissues and the majority of IL-21 producing CD4+ T cells co-expressed IFN-γ or IL-17A. IL-21+IFN-γ+CD4+ T cells in NP tissues exhibited the features of both Tfh and Th1 cells which co-expressed significantly higher amount of CXCR5, ICOS, PD-1, Bcl-6 and T-bet than did IL-21+IFN-γCD4+ T cells. [Sci Rep] Full Article

Quantitative and Qualitative Characterization of Expanded CD4+ T Cell Clones in Rheumatoid Arthritis Patients
Using combination of a single-cell analysis and next-generation sequencing in TCR repertoire analysis, researchers revealed the detailed nature of expanded CD4+ T cell clones by examining peripheral blood from five rheumatoid arthritis (RA) patients and synovium from one RA patient. [Sci Rep] Full Article

mTOR Inhibition Per Se Induces Nuclear Localization of FOXP3 and Conversion of Invariant NKT (iNKT) Cells into Immunosuppressive Regulatory iNKT Cells
Researchers report that the mammalian target of rapamycin (mTOR) inhibitor rapamycin and IL-10, but not TGF-β, can induce FOXP3 expression in iNKT cell lines. [J Immunol] Abstract | Full Article

Progesterone Promotes Maternal-Fetal Tolerance by Reducing Human Maternal T-Cell Polyfunctionality and Inducing a Specific Cytokine Profile
Scientists report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions in potentially deleterious IFN-γ and TNF-α production but also reductions in IL-10 and IL-5. Conversely, production of IL-4 was increased. [Eur J Immunol] Abstract

1α,25-DihydroxyvitaminD3 Acts via TGFβ to Upregulate Expression of Immunosuppressive CD73 on Human CD4+Foxp3 T Cells
Researchers investigated the direct impact of vitamin D (1α,25-dihydroxyvitaminD3) on expression of the downstream ecto-5’-nucleotidase CD73 by human CD4 T cells, and components of the TGFβ pathway which have been implicated in the modulation of CD73 by murine T cells. [Immunology] Abstract

Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro
The effect of dicarbonyl on defensin peptide structure was tested by exposing recombinant human β-defensin-2 (rhBD-2) to methylgloxal or glyoxal with subsequent analysis by MALDI-TOF MS and LC/MS/MS. The effect of dicarbonyl on rhBD-2 chemotactic function was determined by chemotaxis assay in CEM-SS cells. [PLoS One] Full Article | Press Release

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Immunopathology of Multiple Sclerosis
Investigators discuss the current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still unanswered. [Nat Rev Immunol] Abstract

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Immune Design and Merck to Collaborate on Combination Trials of Two Immune Design Immunotherapies with Merck’s KEYTRUDA® for Non-Hodgkin’s Lymphoma and Melanoma
Immune Design announced it has entered into clinical collaboration agreements through subsidiaries of Merck to evaluate the safety and efficacy of two immune design immuno-oncology investigative agents, G100 and LV305, separately combined with KEYTRUDA®, Merck’s anti-PD-1 therapy, in Phase I trials in patients with non-Hodgkin’s lymphoma and melanoma, respectively. [Merck & Co., Inc] Press Release

Sanofi, Evotec and Apeiron Biologics Enter Collaboration to Develop Novel Small Molecule Immuno-Oncology Treatments
Sanofi announced that it has entered a research collaboration and license agreement with Evotec and Apeiron Biologics to discover and develop first-in-class small molecule-based immuno-oncology therapies to treat solid and hematological cancers by enhancing the anti-tumor activity of the human immune system. [Sanofi] Press Release

Medimmune Enters into Strategic Cancer Vaccine Collaboration and License Agreement with Inovio Pharmaceuticals
AstraZeneca announced that MedImmune, its global biologics research and development arm, has entered into a license agreement and collaboration with Inovio Pharmaceuticals, a biotechnology company developing DNA-based immunotherapies for cancer and infectious diseases. [AstraZeneca] Press Release

Newcastle Gets £5 Million to Boost Drug Development
Cancer Research UK’s Drug Discovery Committee has awarded Newcastle University’s Northern Institute of Cancer Research £5 million to bring more cancer drugs to clinical trials. [Cancer Research UK] Press Release

Cancer Research Institute to Honor Outstanding Contributions to Basic and Tumor Immunology Research
The Cancer Research Institute will bestow its highest honors on three scientists who have made fundamental contributions to the fields of immunology and cancer immunotherapy. [Cancer Research Institute] Press Release

Argos Therapeutics Announces Pilot Clinical Trial of AGS-003 as Neoadjuvant Immunotherapy for Localized Renal Cell Carcinoma
Argos Therapeutics Inc. announced the initiation of a single-center pilot clinical trial of AGS-003 as a neoadjuvant immunotherapy in patients with localized renal cell carcinoma. The study is being conducted at Roswell Park Cancer Institute and is designed to enroll a maximum of ten patients who will be treated with AGS-003 before nephrectomy in order to assess immune system response and tumor effects. [Argos Therapeutics Inc.] Press Release

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European Medicines Agency (European Union)

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Therapeutic Goods Administration (Australia)
NEW 45th Annual Scientific Meeting of the Australasian Society for Immunology
November 29-December 3, 2015
Canberra, Australia

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NEW Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Scientific Marketing Specialist – Immunology (STEMCELL Technologies Inc.)

Faculty Positions – Stem Cell/Immunology/Medical Virology (Hallym University Medical Center)

Postdoctoral Fellow – Biotechnology (Qu Biologics Inc.)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Positions – Cancer Research (Rutgers University)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate (Editas Medicine)

Postdoctoral Researcher – Immunology (New York University School of Medicine)

Postdoctoral Fellow – Immunology (Cellectis Inc.)

Postdoctoral Fellowship – Immunology (Huazhong University of Science and Technology)

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