Immune Regulation News Volume 11.32 | Aug 30 2019

TOP STORY

Notch and the Pre-TCR Coordinate Thymocyte Proliferation by Induction of the SCF Subunits Fbxl1 and Fbxl12

Researchers found that β-selection-associated proliferation required the combined activity of two Skp-cullin-F-box (SCF) ubiquitin ligase complexes that included as substrate recognition subunits the F-box proteins Fbxl1 or Fbxl12. [Nat Immunol] Abstract

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Differential Activation of the Transcription Factor IRF1 Underlies the Distinct Immune Responses Elicited by Type I and Type III Interferons

Type I and III interferons (IFNs) displayed kinetic differences in expression of IFN-stimulated genes and proinflammatory responses, with type I IFNs preferentially stimulating expression of the transcription factor IRF1. [Immunity] Abstract | Graphical Abstract

Blood-Brain Barrier Permeable Nano Immunoconjugates Induce Local Immune Responses for Glioma Therapy

Investigators describe targeted nanoscale immunoconjugates on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the blood-brain barrier and activation of local brain anti-tumor immune response. [Nat Commun] Full Article

A Next-Generation Tumor-Targeting IL-2 Preferentially Promotes Tumor-Infiltrating CD8⁺ T-Cell Response and Effective Tumor Control

The authors constructed a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhanced antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes. [Nat Commun] Full Article

IL-2 Production by Self-Reactive CD4 Thymocytes Scales Regulatory T Cell Generation in the Thymus

Investigators report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. [J Exp Med] Abstract

The Nuclear Receptor REV-ERBα Modulates Th17 Cell-Mediated Autoimmune Disease

Scientists identified REV-ERBα, a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonized RORγt function in Th17 cells. [Proc Natl Acad Sci USA] Full Article

The Metabolic Regulator Lamtor5 Suppresses Inflammatory Signaling via Regulating mTOR-Mediated TLR4 Degradation

Investigators identified an unexpected role of Lamtor5, a newly identified component of the amino acid-sensing machinery, in modulating TLR4 signaling and controlling inflammation. [Cell Mol Immunol] Abstract

Essential Roles of S100A10 in Toll-Like Receptor Signaling and Immunity to Infection

Researchers demonstrated an essential function of S100A10 in Toll-like receptor (TLR) signaling. S100A10 was constitutively expressed in macrophages, but was significantly downregulated upon TLR activation. [Cell Mol Immunol] Abstract

SMAC Mimetics Promote NIK-Dependent Inhibition of CD4⁺ T_H17 Cell Differentiation

The authors found that treatment of CD4⁺ T cells with second mitochondria-derived activator of caspase (SMAC) mimetics during T helper 17 (T_H17) cell differentiation disrupted the balance between two antagonistic transcription factor modules. [Sci Signal] Abstract

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Dendritic Cells in Cancer Immunology and Immunotherapy

The authors outline how different dendritic cell subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies. [Nat Rev Immunol] Abstract

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Anifrolumab Phase III Trial Meets Primary Endpoint in Systemic Lupus Erythematosus

AstraZeneca announced that the Phase III TULIP 2 trial for anifrolumab, a potential new medicine for the treatment of systemic lupus erythematosus, met its primary endpoint, achieving a statistically-significant and clinically-meaningful reduction in disease activity versus placebo, with both arms receiving standard of care. [AstraZeneca] Press Release

Adaptimmune and Noile-Immune Announce Agreement to Develop SPEAR T-Cell Products expressing IL-7 and CCL19 as a Next-Generation Treatment for Cancer Patients

Adaptimmune Therapeutics plc and Noile-Immune Biotech, Inc. announced that they will co-develop next-generation SPEAR T-cell products, incorporating Noile-Immune’s PRIME (proliferation inducing and migration enhancing) technology, based upon co-expression of IL-7 and CCL19. [Adaptimmune Therapeutics plc] Press Release

PIONYR Immunotherapeutics Announces Key Leadership Team Addition and Clinical Candidates Targeting Tumor-Associated Macrophages

PIONYR announced that its lead development candidates, PY314 and PY159 targeting TREM2 and TREM1, respectively, are on track to complete IND-enabling studies and are expected to enter clinical development in 2020. [PIONYR Immunotherapeutics, Inc. (PR Newswire Association LLC.)] Press Release

American Neuromuscular Foundation Awards CIDP-Focused Clinical Research Fellowship

The American Neuromuscular Foundation has a new chronic inflammatory demyelinating polyneuropathy (CIDP) development grant award recipient, Dr. Karissa Gable. [The American Neuromuscular Foundation (Newswise, Inc.)] Press Release

OncoNano Awarded $15.4 Million Grant from Cancer Prevention and Research Institute of Texas

OncoNano Medicine, Inc. announced that it has been awarded $15.4 million from the Cancer Prevention and Research Institute of Texas to advance ONM-500, one of OncoNano’s innovative oncology product candidates. [OncoNano Medicine, Inc.] Press Release

Younger Scientists Need Better Support

Letters from research funders to university leaders rarely raise eyebrows. But a letter sent this month by the heads of the United Kingdom’s three largest medical-research funders did just that. [Nature News] Editorial

Memo to Italy’s President: Your Researchers Need You

Italy’s coalition government ended abruptly, when the nationalist Lega party of deputy prime minister Matteo Salvini announced that it was walking away from its turbulent coalition with the anti-establishment M5S party, known as the Five Star Movement. The collapse is of great concern: a much-delayed funding increase is now on hold, and the political uncertainty adds further threat. [Nature News] Editorial

NSF Graduate Fellowships Disproportionately Go to Students at a Few Top Schools

As this year’s eligible students begin to labor over their applications, it’s worth asking why certain schools come away with dozens of winners each year—and what that means about the academy at large. [ScienceInsider] Editorial

NEW 40^th European Workshop for Rheumatology Research (EWRR)
February 13-16, 2020
Leuven, Belgium

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NEW Faculty Position – Tumor Immunology (University of Utah)

Research Technologist (STEMCELL Technologies Inc.)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Assistant Professor and Postdoctoral Fellows – Immunology (Chinese Academy of Sciences)

Laboratory Manager – Human Immunology (Karolinska Institutet)

Postdoctoral Position – Cell Death, Inflammation and Immunity (University Hospital of Cologne)

Professorship – Innate Immunity and Cardiovascular Repair (Goethe University Frankfurt am Main)

Staff Scientist – Lead Immunotherapy Bioinformatician (Fred Hutchinson Cancer Research Center)

Assistant Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Position – Computational Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Quantitative Microscopy of Immune Cells (National Institute on Aging)

Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Fellow – TCR Immunology/Immune Therapy (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

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