Volume 8.09 | Mar 11

Immune Regulation News 8.09 March 11, 2016
Immune Regulation News
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Protein Increases Signals that Protect Cancer Cells
A cancer-associated protein called Myc directly controls the expression of two molecules known to protect tumor cells from the host’s immune system. [Press release from Stanford Medicine discussing online publication in Science] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory
Scientists used a combination of Aicda and antibody mutant alleles that separate the effects of class-switch recombination and somatic hypermutation on polyclonal immune responses. They found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center. [Immunity] Abstract

A Molecular Threshold for Effector CD8+ T Cell Differentiation Controlled by Transcription Factors Blimp-1 and T-Bet
Using genetic approaches and transcriptional profiling of antigen-specific CD8+ T cells, the authors revealed a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. [Nat Immunol] Abstract

Itk Is Required for Th9 Differentiation via TCR-Mediated Induction of IL-2 and IRF4
Researchers showed that Itk, a mediator of T cell receptor signaling required for Th2 immune responses and the development of asthma, is a positive regulator of Th9 differentiation. In a model of allergic lung disease, Itk-deficient mice show reduced pulmonary inflammation and interleukin (IL)-9 production by T cells and innate lymphoid type 2 cells (ILC2), despite normal early induction of ILC2s. [Nat Commun] Full Article

Autoantibody-Boosted T-Cell Reactivation in the Target Organ Triggers Manifestation of Autoimmune CNS Disease
Researchers report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. [Proc Natl Acad Sci USA] Abstract

Sialic Acid-Modified Antigens Impose Tolerance via Inhibition of T-Cell Proliferation and De Novo Induction of Regulatory T Cells
Scientists demonstrated that modification of antigens with sialic acids (Sia-antigens) regulates the generation of antigen-specific regulatory T cells via dendritic cells (DCs). Additionally, DCs that take up Sia-antigen prevent formation of effector CD4+ and CD8+ T cells. [Proc Natl Acad Sci USA] Abstract | Full Article

The Adhesion Molecule PECAM-1 Enhances the TGF-β–Mediated Inhibition of T Cell Function
Researchers found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) transforming growth factor–β (TGF-β) signaling in T cells. [Sci Signal] Abstract | Editorial

Intralymphatic mRNA Vaccine Induces CD8 T-Cell Responses that Inhibit the Growth of Mucosally Located Tumors
Scientists demonstrated that E7-TriMix mRNA vaccine-induced CD8+ T lymphocytes migrate into the tumor nest and control tumor growth, although they do not express mucosa-associated markers such as CD103 or CD49a. They also showed that despite the presence of the antigen-specific T cells in the tumor lesions, the therapeutic outcomes in the genital tract model remain limited. [Sci Rep] Full Article

NAD+ Regulates Treg Cell Fate and Promotes Allograft Survival via a Systemic IL-10 Production that Is CD4+ CD25+ Foxp3+ T Cells Independent
Scientists investigated the impact of NAD+ on the fate of CD4+ CD25+ Foxp3+ Tregs in-depth, dissected their transcriptional signature profile and explored mechanisms underlying their conversion into IL-17A producing cells. [Sci Rep] Full Article

Alkaline Ceramidase 3 Deficiency Aggravates Colitis and Colitis-Associated Tumorigenesis in Mice by Hyperactivating the Innate Immune System
Investigators demonstrated that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells . [Cell Death Dis] Full Article

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Development of Immuno-Oncology Drugs — from CTLA4 to PD1 to the next Generations
The author summarizes the recent history of cancer immunotherapy, including the factors that led to its success, provides an overview of novel drug-development considerations, summarizes three generations of immunotherapies that have been developed since 2011 and illustrates the breadth of opportunities these new generations of immunotherapies represent. [Nat Rev Drug Discov] Abstract

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Heat Biologics Presents Positive ComPACT Preclinical Data at the Keystone Symposia
Heat Biologics, Inc. announced that positive preclinical data from its next generation ComPACT platform technology, which combines a T cell priming vaccine and T cell co-stimulator in a single product, were presented. [Press release from Heat Biologics, Inc. discussing research presented at the Keystone Symposia on Cancer Vaccines: Targeting Cancer Genes for Immunotherapy, Whistler] Press Release | Abstract

Combination of Lapatinib and Trastuzumab Shrinks HER2 Positive Breast Cancer Significantly in 11 Days after Diagnosis
Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumors shrink significantly or even disappear, according to results from a clinical trial. [Press release from The University of Manchester discussing research presented at the 10th European Breast Cancer Conference (EBCC-10), Amsterdam] Press Release

Biothera Pharmaceuticals to Present Its Phase II Cancer Immunotherapy Data
Biothera Pharmaceuticals Inc. presented data on its Phase II cancer immunotherapy Imprime PGG, the company’s first-in-class, systemically administered beta glucan PAMP (pathogen associated molecular patterning molecule). [Press release from Biothera Pharmaceuticals Inc. discussing research presented at the Molecular Medicine Tri-Conference 2016, San Francisco] Press Release

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Data and Safety Monitoring Board Recommends Advance of Current DC Vaccine Clinical Trial in AML into Phase II
Medigene AG announced the successful recruitment of the planned patients for Phase I of its current clinical trial of dendritic cell (DC) vaccines in acute myeloid leukemia (AML). [Medigene AG] Press Release

Advaxis Truly Personalized Cancer Immunotherapy Moves Forward with Signing of an Exclusive Supply Agreement with Synthetic Genomics for Synthetic DNA
Advaxis, Inc. and SGI-DNA announced that the companies have entered into a five-year exclusive supply agreement. Under the terms of the agreement, SGI-DNA will manufacture for Advaxis synthetic DNA which will be used in Advaxis’ personalized Listeria monocytogenes (Lm)-based immunotherapy, known as MINE™ (My Immunotherapy Neo-Epitopes). [Advaxis, Inc.] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Advances in Immuno-Oncology Congress 2016
May 12-13, 2016
London, United Kingdom

NEW Banff Conference on Infectious Diseases 2016
June 1-4, 2016
Banff, Canada

Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Position or Research Scientist – Mucosal Immunology (Qu Biologics)

NEW Immunologist (GlaxoSmithKline plc)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Single Cell Analysis of Human T Cell Development (Ghent University)

Postdoctoral Fellow – Clinical Immunology (Benaroya Research Institute at Virginia Mason)

Postdoctoral Fellow – Autoimmune, Inflammatory and Demyelinating Diseases (Queen’s University Belfast)

Postdoctoral Positions – Innate Immunity and Autoimmunity (UT Southwestern Medical Center)

Faculty Positions – Immunology (University of Texas Health Science Center)

Senior Scientist – Immunology (Bavarian Nordic GmbH)

Assistant or Associate Professor – Immunity and Tolerance (Cincinnati Children’s Hospital Medical Center)

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