Volume 7.14 | Apr 24

Immune Regulation News 7.14 April 24, 2015
Immune Regulation News
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Newly Discovered Pathway Reveals How Our Immune System Is Regulated; Gives Hope for Serious Chronic Diseases
Researchers have identified an important new way in which our immune systems are regulated, and hope that understanding it will help tackle the debilitating effects of type 1 diabetes, rheumatoid arthritis and other serious diseases. The team discovered a novel pathway that regulates the movement of pathogenic immune cells from the blood into tissue during an inflammatory response. [Press release from the University of Birmingham discussing online prepublication in Nature Medicine] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Immunosurveillance of the Liver by Intravascular Effector CD8+ T Cells
Effector CD8+ T cells play a key role during hepatotropic viral infections. Investigators used advanced imaging in mouse models of hepatitis B virus pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. [Cell] Abstract | Graphical Abstract

The Transcription Factor Lymphoid Enhancer Factor 1 Controls Invariant Natural Killer T Cell Expansion and Th2-Type Effector Differentiation
Researchers demonstrated a unique function for the transcription factor lymphoid enhancer factor 1 in the postselection expansion of invariant natural killer T cells through a direct induction of the CD127 component of the receptor for interleukin-7 and the transcription factor c-myc. [J Exp Med] Abstract

mir-17-92 Regulates Bone Marrow Homing of Plasma Cells and Production of Immunoglobulin G2c
Scientists ablated mir-17-92 in mature B cells and demonstrated that mir-17-92 is dispensable for conventional B-cell development in the periphery. mir-17-92-deficiency in B cells led to enhanced homing of plasma cells to the bone marrow during T-cell-dependent immune response and selectively impaired immunoglobulin G2c production. [Nat Commun] Abstract

NK Cells Require IL-28R for Optimal In Vivo Activity
IL-28R-deficient mice were more susceptible to growth of the natural killer (NK) cell-sensitive lymphoma. Specific loss of IL-28R in NK cells transferred into lymphocyte-deficient mice resulted in reduced LPS-induced IFN-γ levels and enhanced tumor metastasis. [Proc Natl Acad Sci USA] Abstract

Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation
Investigators directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR. Ectopic expression of RAS homologue enriched in the brain increased mTOR complex 1 signaling, promoted a switch to aerobic glycolysis and increased expansion of effector T cells. [Cancer Res] Abstract | Full Article

Intratumoral Myeloid Cells Regulate Responsiveness and Resistance to Antiangiogenic Therapy
Investigators found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in mouse models of pancreatic neuroendocrine and mammary tumors. Tumors reinitiated angiogenesis and immune suppression by activating PI3K signaling in all CD11b+ cells, rendering tumors nonresponsive to VEGF/VEGFR inhibition. [Cell Rep] Full Article | Graphical Abstract

Astrocyte-Derived TGF-β1 Accelerates Disease Progression in ALS Mice by Interfering with the Neuroprotective Functions of Microglia and T Cells
Scientists identified transforming growth factor-β1 (TGF-β1) as a negative regulator of neuroprotective inflammatory response. They demonstrated that astrocyte-specific overproduction of TGF-β1 in SOD1G93A mice accelerated disease progression in a non-cell-autonomous manner, with reduced IGF-I production in deactivated microglia and fewer T cells with an IFN-γ-dominant milieu. [Cell Rep]
Full Article | Graphical Abstract

B Cell Antigen Presentation Is Sufficient to Drive Neuroinflammation in an Animal Model of Multiple Sclerosis
Researchers found that B cells cooperated with dendritic cells to enhance experimental autoimmune encephalomyelitis (EAE) severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. [J Immunol] Abstract

Survival and Maintenance of Regulatory T Cells Require the Kinase TAK1
Investigators showed that regulatory T (Treg)-conditional ablation of the kinase TAK1 reduced the number of Treg cells in the peripheral lymphoid organs, causing abnormal activation of conventional T cells and autoimmune symptoms. Using an inducible gene knockout approach, they further demonstrated that TAK1 is crucial for the survival of Treg cells. [Cell Mol Immunol] Abstract

Involvement of RORγT-Overexpressing T Cells in the Development of Autoimmune Arthritis in Mice
Researchers determined the role of transcription retinoid-related orphan receptor gamma t (RORγt) expression in T cells on the development of collagen-induced arthritis (CIA). Methods CIA was induced in C57BL/6 and T cell-specific RORγt transgenic mice. [Arthritis Res Ther] Abstract | Full Article

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The Evolving Paradigm of Cell-Nonautonomous UPR-Based Regulation of Immunity by Cancer Cells
The authors review the role of cell-extrinsic effects on innate and adaptive immunity, suggesting that the transmission of endoplasmic reticulum stress from cancer cells to myeloid cells in particular is an expedient used by cancer cells to control the immune microenvironment, which acquires pro-inflammatory as well as immune-suppressive characteristics. [Oncogene] Full Article

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Celldex’s Varlilumab Demonstrates Synergistic Anti-Tumor Activity with PD-1 Signaling Blockade in Preclinical Studies
Celldex Therapeutics, Inc. announced preclinical results that further support varlilumab’s expansion into combination studies with PD-1 inhibitors. [Press release from Celldex Therapeutics, Inc. discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Inflammation-Cancer Feedback Loop Discovery Is a Step Toward Better Cancer Drugs
New findings hidden within the complex machinery behind the vicious cycle of chronic inflammation and cancer were presented by the University of Pittsburgh Cancer Institute. [Press release from the University of Pittsburgh discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

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MedImmune and Juno Therapeutics Announce Immuno-Oncology Clinical Trial Collaboration
MedImmune and Juno Therapeutics, Inc. announced that they have entered into a new collaboration to conduct combination clinical trials in immuno-oncology with one of Juno’s investigational CD19-directed chimeric antigen receptor T cell candidates and MedImmune’s investigational programmed cell death ligand 1 immune checkpoint inhibitor, MEDI4736. [Juno Therapeutics, Inc.] Press Release

Effimune Obtains Regulatory Approval for Phase I Clinical Trial in Humans of Its New Immunomodulator FR104
Effimune announced that it had received the authorization for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system. [Effimune] Press Release

Pfizer and Provectus Biopharmaceuticals Receive Patent Allowance for Use of PV-10 in Combination with Systemic Immunotherapy Agents in Treatment of Cancer
Provectus Biopharmaceuticals, Inc. announced that it has received from the US Patent and Trademark Office a Notice of Allowance for a joint patent application made with Pfizer, Inc. The patent will protect use of PV-10 in combination with certain other types of drugs in the treatment of melanoma and cancers of the liver. [Provectus Biopharmaceuticals, Inc.] Press Release
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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 Gordon Research Conference: Apoptotic Cell Recognition and Clearance
June 14-19, 2015
Biddeford, United States

NEW Keystone Symposium – Autophagy
June 19-24, 2015
Breckenridge, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Fellow – Immunology (Boston Children’s Hospital)

NEW Postdoctoral Position – Immunology-Vaccinology (Université de Liège)

Postdoctoral Fellow – Genomic and Immunogenomic Aspects of Lymphomas (University of Chicago)

Principal Scientist – Antibody Discovery, Biologics Research (Janssen Research & Development LLC.)

Postdoctoral Fellow – Immunopathogenesis of Multiple Sclerosis (University of Iowa)

Senior Scientist – Immunology (National Institute of Immunology)

Assistant Professor – Immunology (Northwestern University)

Assistant Professor – Immunology (Dana-Farber Cancer Institute)

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