Volume 8.06 | Feb 19

Immune Regulation News 8.06 February 19, 2016
Immune Regulation News
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Researchers Discover New Approach to Treating Autoimmune Diseases
Using animal models and human cells in animal models, researchers have discovered a novel mechanism that stops the immune attack, and have developed a new class of drugs that harnesses this mechanism to treat various autoimmune diseases without compromising the entire immune system. [Press release from the University of Calgary discussing online publication in Nature] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Visualizing Antibody Affinity Maturation in Germinal Centers
By combining multiphoton microscopy and sequencing, researchers showed that tens to hundreds of distinct B cell clones seed each germinal center (GC) and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. [Science] Abstract | Press Release

Transient Inhibition of ROR-γT Therapeutically Limits Intestinal Inflammation by Reducing TH17 Cells and Preserving Group 3 Innate Lymphoid Cells
Scientists demonstrated that transient chemical inhibition of RAR-related orphan receptor-γt (ROR-γt) in mice selectively reduces cytokine production from T helper 17 (TH17) but not innate lymphoid cells in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. [Nat Med]
Abstract | Press Release

CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation
Scientists demonstrated that differentiation of tumor-associated macrophages in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. [Immunity] Abstract | Graphical Abstract | Press Release

Glycogen Synthase Kinase 3 Inactivation Drives T-Bet-Mediated Downregulation of Co-Receptor PD-1 to Enhance CD8+ Cytolytic T Cell Responses
Researchers identified glycogen synthase kinase 3 (GSK-3) as a key upstream kinase that regulated PD-1 expression in CD8+ T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8+ cytotoxic T lymphocyte function. [Immunity]
Full Article | Graphical Abstract

A Hematopoietic Cell–Driven Mechanism Involving SLAMF6 Receptor, SAP Adaptors and SHP-1 Phosphatase Regulates NK Cell Education
Activation of natural killer (NK) cells by hematopoietic target cells is controlled by the SLAM family of receptors and by the associated SAP family of adaptors. Investigators found that SLAM receptors also enhanced NK cell activation by nonhematopoietic target cells, which lack ligands for SLAM receptors. [Nat Immunol] Abstract

Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution
Tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. [Cell Metab] Full Article | Graphical Abstract | Press Release

TGF-β Inhibits the Activation and Functions of NK Cells by Repressing the mTOR Pathway
Scientists provide genetic, pharmacologic, and biochemical evidence that a critical target of transforming growth factor–β (TGF-β) signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). [Sci Transl Med] Abstract

YY1 Inhibits Differentiation and Function of Regulatory T Cells by Blocking Foxp3 Expression and Activity
Researchers showed that YY1 expression is lower in regulatory T (Treg) cells than Tconv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. [Nat Commun] Full Article

Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels
The authors describe a role for the chemokine CCL21 in intralymphatic dendritic cell (DC) crawling. They found that blockade of CCL21—but not the absence of lymph flow—completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. [Cell Rep] Full Article | Graphical Abstract | Press Release | Video

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Harnessing the Plasticity of CD4+ T Cells to Treat Immune-Mediated Disease
The authors review CD4+ T cell plasticity by examining the molecular mechanisms that regulate it — from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signaling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programs. [Nat Rev Immunol] Abstract

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Dramatic Remissions Seen in Immunotherapy Trial of Blood Cancer Patients
Twenty-seven out of 29 patients with an advanced blood cancer who received an experimental, “living” immunotherapy as part of a clinical trial experienced sustained remissions. [Press release from Fred Hutchinson Cancer Research Center discussing research presented at the American Association for the Advancement of Science (AAAS) Annual Meeting, Washington, DC] Press Release | Video

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Government of Canada Invests in Research Commercialization
The Centre for Commercialization of Cancer Immunotherapy will receive funding of $15 million over five years to develop, translate and commercialize cancer immunotherapy. [Networks of Centres of Excellence of Canada] Press Release

Cancer MoonShot 2020 Announces the Formation of a National Pediatrics Consortium, a Major Milestone in the War on Cancer in Children
Cancer MoonShot 2020 announced another milestone in its quest to alter the course of cancer care with the formation of the Pediatrics Consortium focused on bringing the promise of combined immunotherapy as the next-generation standard of cancer care to children diagnosed with the disease. [Cancer MoonShot 2020] Press Release

Effimune, In Cell Art Launch Cancer Immunotherapy Collaboration
Effimune will use In Cell Art’s Nanotaxi® technology to develop cancer immunotherapies based on producing antibodies from a patient’s body. The companies will compare the efficacy of that approach to traditional production of antibodies through a bioreactor during the 12-month collaboration. [Effimune (Genetic Engineering & Biotechnology News)] Press Release

AVROBIO Inc. Launches to Develop Novel, Clinical-Stage Cell and Gene Therapies Targeting Immuno-Oncology and Rare Diseases
AVROBIO announced its launch plans to accelerate development of two novel cell and gene therapies. Phase I programs will be in the clinic by early to mid-2016 in both acute myeloid leukemia and Fabry disease. [AVROBIO 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 AACR Annual Meeting 2016
April 16-20, 2016
New Orleans, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Fellow – Autoimmune, Inflammatory and Demyelinating Diseases (Queen’s University Belfast)

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

Professor – Dermatology with Special Interest in Allergology and Immunology (Eberhard Karls Universität Tübingen)

Postdoctoral Fellowship – Immunology (Beth Israel Deaconess Medical Center)

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)

Research Associate – Treg Therapy for Multiple Sclerosis (University College London)

Research Associate – T Cell Therapy for Hematological Malignancies (University College London)

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

Postdoctoral Fellow – Cell Therapy (Toronto Western Hospital)

Postdoctoral Position – Immunology (Indiana University)

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