Immune Regulation News Volume 10.12 | Apr 6 2018

TOP STORY

Dimethyl Fumarate Targets GAPDH and Aerobic Glycolysis to Modulate Immunity

Investigators showed that dimethyl fumarate succinates and inactivates the catalytic cysteine of the glycolytic enzyme GAPDH both in vitro and in vivo. It thereby downregulated aerobic glycolysis in activated myeloid and lymphoid cells, which mediated its anti-inflammatory effects. [Science] Abstract

(Ranked by impact factor of the journal)

Co-Inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-Tumor CD8⁺ T Cells

Scientists showed increased B7 superfamily member 1 (B7S1) expression on myeloid cells from human hepatocellular carcinoma correlated with CD8⁺ T cell dysfunction. B7S1 inhibition suppressed development of murine tumors. [Immunity] Abstract | Graphical Abstract

KLRG1⁺ Effector CD8⁺ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity

Using genetic fate mapping analysis of highly cytotoxic KLRG1⁺ effector CD8⁺ T cells, researchers demonstrated that KLRG1⁺ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell lineages, including CX₃CR1^int peripheral memory cells and tissue-resident memory cells. [Immunity] Abstract

MLL5 Suppresses Antiviral Innate Immune Response by Facilitating STUB1-Mediated RIG-I Degradation

Scientists showed that MLL5 suppresses the RIG-I-mediated anti-viral immune response. Mll5-deficient mice infected with vesicular stomatitis virus showed enhanced anti-viral innate immunity, reduced morbidity, and viral load. [Nat Commun] Full Article

Pharmacological Activation of Estrogen Receptor Beta Augments Innate Immunity to Suppress Cancer Metastasis

Investigators showed that the selective estrogen receptor β agonist LY500307 could potently suppress lung metastasis of cancer by recruitment of antitumor neutrophils to the metastatic niche. [Proc Natl Acad Sci USA] Abstract

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases

Scientists examined the utility of a human-specific, GUCY2C-directed scFv as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. [Cancer Immunol Res] Abstract

Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo

Investigators generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8⁺ T lymphocytes expanded moderately better but were less polyfunctional than control cells. [Cell Rep] Full Article | Graphical Abstract

A Hierarchy of Affinities between Cytokine Receptors and the Common Gamma Chain Leads to Pathway Cross-Talk

Investigators report the existence of a fast, cytokine-induced pathway cross-talk acting at the receptor level, resulting from a limiting amount of common gamma chain (γ_c) on the surface of T cells. They found that this limited abundance of γc reduced interleukin-4 (IL-4) and IL-21 responses after IL-7 pre-exposure but not vice versa. [Sci Signal] Abstract

Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells

The authors used multiple mouse models to investigate the regulation of telomerase under oxidative stress as well as its impact on atherogenesis in vitro and in vivo. Using primary lymphocytes and myeloid cell cultures, they demonstrated that cultivation under hyperoxic conditions induced oxidative stress resulting in chronic activation of CD4⁺ cells and significantly reduced CD4⁺ T-cell proliferation. [Arterioscler Thromb Vasc Biol] Abstract

MicroRNA-326 Upregulates B Cell Activity and Autoantibody Production in Lupus Disease of MRL/lpr Mice

Scientists found that miR-326 overexpression in MRL/lpr mice led to B cell hyperactivity and severe systemic lupus erythematosus. Moreover, E26 transformation-specific-1, a negative regulator of B cell differentiation, was identified as a target of miR-326. [Mol Ther Nucleic Acids] Full Article

Critical Role of OX40 Signaling in the TCR-Independent Phase of Human and Murine Thymic Treg Generation

Researchers showed that OX40L is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation in the presence of low-dose IL-2. They hypothesized that OX40 signaling might be integral to the T-cell receptor (TCR)-independent phase of murine and human thymic Treg development. [Cell Mol Immunol] Abstract

The Cish SH2 Domain Is Essential for PLC-γ1 Regulation in TCR Stimulated CD8⁺ T Cells

To study the structural and functional relationships between Cish and PLC-γ1 during CD8⁺ T cell activation, the authors tested mutants of the Cish-SH2 and D/BC domains. [Sci Rep] Full Article

CD4⁺ and CD8⁺ T Cells Exert Regulatory Properties during Experimental Acute Aristolochic Acid Nephropathy

As compared to mice injected with aristolochic acids alone, more severe acute kidney injury was observed after CD4⁺ or CD8⁺ T-cells depletion. TNF-alpha and MCP-1 mRNA renal expressions were also increased. [Sci Rep] Full Article

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Autophagy in Dendritic Cells

An increasing number of recent studies has characterized the involvement of autophagy in dendritic cell (DC) functions in various physiological and pathological contexts. The authors provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology. [Cell Mol Immunol] Full Article

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Siamab Therapeutics to Present New Data on its ST1 Antibody Therapeutic Program Targeting Tumor-Associated STn and STn⁺ Myeloid Derived Suppressor Cells

Siamab Therapeutics, Inc. announced that it will present new research findings for its ST1 monoclonal antibody therapeutic program during a poster presentation. [Press release from Siamab Therapeutics, Inc. (Business Wire, Inc.) discussing research to be presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting, Chicago] Press Release

Boehringer Ingelheim and OSE Immunotherapeutics Announce Global Immuno-Oncology Partnership to Develop a Pioneering Checkpoint Inhibitor for the Treatment of Advanced Solid Tumors

Boehringer Ingelheim and OSE Immunotherapeutics announced a collaboration and exclusive worldwide collaboration and license agreement to jointly develop OSE-172, a SIRP-alpha antagonist targeting myeloid lineage cells. [Boehringer Ingelheim International GmbH] Press Release

FORMA Therapeutics Achieves Key Objective in Collaboration with Celgene Corporation to Advance a Novel Protein Homeostasis Oncology/Immuno-Oncology Program

FORMA Therapeutics announced that it has successfully completed a critical objective under its strategic collaboration agreement with Celgene Corporation, triggering an undisclosed payment from Celgene. [FORMA Therapeutics, Inc.] Press Release

Feinstein Institute, NIH Launch Groundbreaking Clinical Trial for New Lupus Medication

Researchers at Northwell Health’s Feinstein Institute for Medical Research are leading a nationwide National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases sponsored clinical trial testing the efficacy of a synthetic cannabinoid derivative with no psychotropic properties for the treatment of joint inflammation in lupus. [Northwell Health’s Feinstein Institute for Medical Research (PR Newswire Association LLC.)] Press Release

Bioniz Therapeutics Initiates Phase I/II Clinical Study of BNZ-1 in T-Cell Leukemia and Lymphoma

Bioniz Therapeutics, Inc. announced that it has initiated a Phase I/II open-label clinical study of its lead product candidate BNZ-1 in patients with large granular lymphocyte leukemia or refractory cutaneous T-cell lymphoma. [Bioniz Therapeutics, Inc.] Press Release

Why The Ohio State University Decided to Go Public about Misconduct

In an unusual move, The Ohio State University in Columbus released a detailed account of the scientific misbehavior of one of its former faculty members. The 75-page report was damning: It concluded that cancer researcher Ching-Shih Chen—once lauded as an “Innovator of the Year” and the winner of millions of dollars in federal funding—had committed misconduct in eight papers. [ScienceInsider] Editorial

Unnecessary Exclusions Shut Patients Out of Clinical Trials

The FDA will hold a public meeting in Washington to discuss issues related to clinical trial eligibility criteria. Researchers, study sponsors, patients, and the general public will have an opportunity to share their experiences and tell our regulators why it’s time to revisit the guidelines. [STAT News] Editorial

2018 March for Science Will Be Far More than Street Protests

The March for Science has matured. It may even have outgrown its name. [ScienceInsider] Editorial

NEW 5^th European Congress of Immunology (ECI)
September 2-5, 2018
Amsterdam, Netherlands

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

NEW Research Scientist – Biomarker Development (Kymab)

NEW Postdoctoral Research Assistant – Gene Regulation in T Cells (University of Dundee)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immune Suppression Mechanisms in Myeloid Cells (AstraZeneca)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Postdoctoral Position – Tregs in the Hematopoietic Stem Cell Niche (Columbia Center for Translational Immunology)

Scientist – Immune Tolerance (Moderna Therapeutics)

Tenure Track Assistant Professor – Immune Signaling (Technical University of Munich)

Scientist – Immunology (Bioverativ)

Postdoctoral Fellow – Cardiovascular and Immunology Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Research Fellow Position – Immunology Research (ShanghaiTech University)

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