Immune Regulation News Volume 8.13 | Apr 15 2016

A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair
Using multi-channel spinning disk microscopy, researchers identified a rapid pathway of macrophage recruitment into an injured organ via a non-vascular route requiring no maturation from monocytes. [Cell] Abstract | Graphical Abstract | Press Release

Enteric Viruses Ameliorate Gut Inflammation via Toll-Like Receptor 3 and Toll-Like Receptor 7-Mediated Interferon-β Production
The authors found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-β in a TLR3 and TLR7-dependent manner. [Immunity] Abstract | Graphical Abstract

Neutrophils Suppress Intraluminal NK-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells
Researchers defined novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. They showed that CD11b⁺/Ly6G⁺ neutrophils enhance metastasis formation via two distinct mechanisms. [Cancer Discov] Abstract | Full Article

Dendritic Cell Dysfunction and Diabetic Sensory Neuropathy in the Cornea
Investigators used post-wound corneal sensory degeneration and regeneration as a model and tested the hypothesis that diabetes adversely affects DC populations and infiltration, resulting in disrupted DC-nerve communication and diabetic peripheral neuropathy. [J Clin Invest] Full Article | Press Release

IFN-γ Receptor and STAT1 Signaling in B Cells Are Central to Spontaneous Germinal Center Formation and Autoimmunity
Investigators report that B cell–intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for spontaneously developed germinal center (Spt-GC) and follicular T helper cell (Tfh cell) development. They further demonstrated that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. [J Exp Med] Abstract | Press Release

B Cell IFN-γ Receptor Signaling Promotes Autoimmune Germinal Centers via Cell-Intrinsic Induction of BCL-6
Using a chimeric model of B cell-driven autoimmunity, scientists demonstrated that B cell type 1 interferon (IFN) receptor signals accelerate, but are not required for, lupus development. [J Exp Med] Abstract

Clec4A4 Is a Regulatory Receptor for Dendritic Cells that Impairs Inflammation and T-Cell Immunity
Scientists showed that Clec4A4 is a regulatory receptor for the activation of CD8α⁻ conventional dendritic cells (cDCs) that impairs inflammation and T-cell immunity. Clec4a4^−/−CD8α⁻ cDCs showed enhanced cytokine production and T-cell priming following Toll-like receptor-mediated activation. [Nat Commun] Full Article

TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-Cell Persistence and Rejection of Established Tumors
Investigators demonstrated that inactivation of the PD-1 gene in melanoma-reactive CD8⁺ T cells and in fibrosarcoma-reactive polyclonal T cells enhanced the persistence of PD-1 gene-modified T cells at the tumor site and increased tumor control. [Cancer Res] Full Article | Press Release

Neuron-Specific SALM5 Limits Inflammation in the CNS via Its Interaction with HVEM
Researchers found that synaptic adhesion-like molecule 5 (SALM5) suppressed lipopolysaccharide-induced inflammatory responses in the central nervous system (CNS) and that a SALM-specific monoclonal antibody promoted inflammation in the CNS, and thereby aggravated clinical symptoms of mouse experimental autoimmune encephalomyelitis. [Sci Adv] Full Article | Press Release

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Immunotherapy with Live Bacterium Improves Response Rate in Malignant Pleural Mesothelioma
Immunotherapy with a live bacterium combined with chemotherapy demonstrated more than 90% disease control and 59% response rate in patients with malignant pleural mesothelioma, according to the results of a Phase Ib trial. [Press release from the European Society for Medical Oncology discussing research presented at the 2016 European Lung Cancer Conference (ELCC), Geneva] Press Release

Patients with EGFR Expressing Non-Small-Cell Lung Cancer Benefit Most from Necitumumab Added to Chemotherapy
Patients with epidermal growth factor receptor (EGFR) expressing advanced squamous non-small-cell lung cancer benefit most from necitumumab added to gemcitabine and cisplatin chemotherapy, according to a subgroup analysis from the SQUIRE trial. [Press release from the European Society for Medical Oncology discussing research presented at the 2016 European Lung Cancer Conference (ELCC), Geneva] Press Release

Osimertinib Combined with Durvalumab in EGFR-Mutant Non-Small-Cell Lung Cancer
Encouraging clinical activity was demonstrated by the combination of osimertinib plus durvalumab in patients with advanced non-small-cell lung cancer that had received prior treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and also in EGFR-TKI naive patients that was offset by safety observations over the occurrence of interstitial lung disease in some patients. [Press release from the European Society for Medical Oncology discussing research presented at the 2016 European Lung Cancer Conference (ELCC), Geneva] Press Release

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UCLA Joins Collaboration to Advance Cancer Immunotherapy Research
UCLA has joined forces with five of the nation’s other leading cancer centers and The Parker Institute for Cancer Immunotherapy to maximize the potential of cancer immunotherapy research. [UCLA] Press Release

NEOVACS Obtains South Korea Health Authority Approval for IND Application with IFNα Kinoid in Lupus
NEOVACS announced that South Korea health authority approved Neovacs’s Investigational new drug application for IFNα Kinoid in Phase IIb development in Lupus. [NEOVACS] Press Release

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

NEW Junior Group Leader – Immunology (Laboratory of Excellence)

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

Engineering Project Lead (Cytonome)

Postdoctoral Fellowship – Immune Informatics (University of Oslo)

PhD Positions – Cancer Immune Metabolism (University of Erlangen-Nuernberg)

Single Cell Immunologist (Berkeley Lights, Inc.)

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

Postdoctoral Position or Research Scientist – Mucosal Immunology (Qu Biologics)

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