Immune Regulation News Volume 8.15 | Apr 29 2016

Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage
Researchers found that autoimmune regulator (Aire) enforces immune tolerance by ensuring that distinct autoreactive T cell specificities differentiate into the regulatory T (Treg) cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells. [Immunity] Abstract | Graphical Abstract

Inflammatory Triggers Associated with Exacerbations of COPD Orchestrate Plasticity of Group 2 Innate Lymphoid Cells in the Lungs
Scientists found that group 2 innate lymphoid cells (ILCs) exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ. [Nat Immunol]
Abstract | Press Release

Glucose and Glutamine Fuel Protein O-GlcNAcylation to Control T Cell Self-Renewal and Malignancy
Researchers found that glutamine and glucose fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. [Nat Immunol] Abstract | Press Release

Epithelium-Generated Neuropeptide Y Induces Smooth Muscle Contraction to Promote Airway Hyperresponsiveness
Researchers showed that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness without eosinophilic inflammation. [J Clin Invest]
Full Article | Press Release 1 | Press Release 2

Aeroallergen-Induced IL-33 Predisposes to Respiratory Virus-Induced Asthma by Dampening Anti-Viral Immunity
Scientists elucidated the pathogenic processes that underlie the synergistic interplay between allergen exposures and viral infections. Mice were inoculated with a murine-specific Pneumovirus and exposed to low-dose cockroach extract in early- and later-life, and airway inflammation, remodeling and hyperreactivity assessed. Mice were treated with anti-IL-33 or apyrase to neutralize or block the release of IL-33. [J Allergy Clin Immunol] Abstract

Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-Viral CD8⁺ T Cell Responses
Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8⁺ T cell responses more efficiently in vitro and in vivo. [Cell Rep] Full Article | Graphical Abstract

Proteomic Dissection of LPS-Inducible, PHF8-Dependent Secretome Reveals Novel Roles of PHF8 in TLR4-Induced Acute Inflammation and T Cell Proliferation
Using combined approaches to analyze endotoxin (LPS)-induced changes in both gene-specific transcription and protein secretion to the extracellular compartment, investigators characterized novel functions of the lysine demethylase PHF8 as a pro-inflammatory, gene-specific chromatin regulator. [Sci Rep] Full Article

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Memory CD8⁺ T Cells: Innate-Like Sensors and Orchestrators of Protection
Memory CD8⁺ T cells emerge as early sensors of danger signals, mediating protective immunity both through licensing of cellular effectors of the innate immune system and via the canonical functions associated with memory T cells. The authors discuss implications for the development of T cell vaccines and therapies and highlight important areas in need of further investigation. [Trends Immunol] Abstract

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New Preclinical Study Shows Immunovaccine’s DepoVax™-Based Cancer Vaccine May Improve Efficacy of Checkpoint Inhibitors
Immunovaccine Inc. showed that a combination immunotherapy using a DepoVax™-based vaccine could enhance the anti-tumor effects of a PD-1 blockade, controlling growth in advanced HPV-expressing tumors in animal models. [Press release from Immunovaccine, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Intensity Therapeutics Reports that INT230-6’s Anti-Cancer Mechanism Is a Combination of Cell Death with Immune System Activation
Intensity Therapeutics presented research that indicates that INT230-6 induces significant cancer cell death in the tumor microenvironment. Thereafter, eradication of the tumor by INT230-6 requires T lymphocytes and leads to a potent and durable systemic anti-cancer T-cell-dependent immunity against the tumor. [Press release from Intensity Therapeutics, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Heat Biologics and OncoSec Present Data
Heat Biologics, Inc. announced that preclinical data from its collaboration with OncoSec Medical Incorporated focused on evaluating the combination of immunotherapy platforms were presented. [Press release from Heat Biologics, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Juno’s Investigational CAR T Cell Product Candidates JCAR018 and JTCR016 Demonstrate Encouraging Clinical Responses in Patients with B-Cell and Mesothelioma Cancers
Juno Therapeutics, Inc. announced, in partnership with its collaborators, early clinical data from two oral presentations for two product candidates. [Press release from Juno Therapeutics, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

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FDA Grants Advaxis Fast Track Designation for ADXS-HER2 for Patients with Newly-Diagnosed, Non-Metastatic, Surgically-Resectable Osteosarcoma
Advaxis, Inc. announced that the Food and Drug Administration (FDA) has granted Fast Track Designation for the company’s immunotherapy product candidate ADXS-HER2 for patients with newly-diagnosed, non-metastatic, surgically-resectable osteosarcoma. [Advaxis, Inc.] Press Release

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)

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NEW Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

NEW Faculty Positions – Microbiology and Immunology (National University of Singapore)

NEW Postdoctoral Fellow – Immunology (Erasmus MC)

Scientist – Bioengineering (STEMCELL Technologies Inc.)

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

PhD Positions – Cancer Research (German Cancer Research Center)

Faculty Positions – Immunology and Host-Microbe Interactions (Ohio State University)

Junior Group Leader – Immunology (Laboratory of Excellence)

Engineering Project Lead (Cytonome)

Postdoctoral Fellowship – Immune Informatics (University of Oslo)

Single Cell Immunologist (Berkeley Lights, Inc.)

Postdoctoral Researchers – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

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