Immune Regulation News Volume 11.14 | Apr 26 2019

TOP STORY

Compartmentalized Gut Lymph Node Drainage Dictates Adaptive Immune Responses

Researchers showed that gut-draining lymph nodes (gLNs) were immunologically specific to the functional gut segment that they drain. Stromal and dendritic cell gene signatures and polarization of T cells against the same luminal antigen differed between gLNs, with the proximal small intestine-draining gLNs preferentially giving rise to tolerogenic responses and the distal gLNs to pro-inflammatory T cell responses. [Nature] Abstract

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Immunogenic Neoantigens Derived from Gene Fusions Stimulate T Cell Responses

Scientists demonstrated that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. They identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. [Nat Med] Abstract

The AKT Kinase Signaling Network Is Rewired by PTEN to Control Proximal BCR Signaling in Germinal Center B Cells

The authors describe a germinal center (GC)-specific, AKT-kinase-driven negative feedback loop that attenuates B cell antigen receptor (BCR) signaling. Mass spectrometry revealed that AKT target activity was altered in GC B cells compared with naive B cells. [Nat Immunol] Abstract

Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production

Investigators found that Toll-like receptor activation enhanced choline uptake by macrophages and microglia through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline phosphorylation attenuated NLRP3 inflammasome activation and IL-1β and IL-18 production in stimulated macrophages. [Cell Metab] Abstract | Graphical Abstract

Activation of Mast-Cell-Expressed Mas-Related G-Protein-Coupled Receptors Drives Non-Histaminergic Itch

Researchers report that mast cell activation via Mas-related G-protein-coupled receptor b2 evoked non-histaminergic itch in mice independently of the IgE-Fc epsilon RI-histamine axis. [Immunity] Abstract | Graphical Abstract

Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion

Tape stripping mouse skin, a surrogate for scratching, caused expansion and activation of small intestinal mast cells, increased intestinal permeability, and promoted food anaphylaxis in sensitized mice. [Immunity] Abstract | Press Release | Graphical Abstract

Galectin-3, a Novel Endogenous TREM2 Ligand, Detrimentally Regulates Inflammatory Response in Alzheimer’s Disease

Galectin-3 (Gal3) deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar amyloid beta. [Acta Neuropathol] Full Article

Mettl3-Mediated mRNA m⁶A Methylation Promotes Dendritic Cell Activation

The authors report that RNA methyltransferase Mettl3-mediated mRNA N6-methyladenosine (m⁶A) methylation promoted dendritic cell activation and function. [Nat Commun] Full Article

Sorafenib Induces Pyroptosis in Macrophages and Triggers NK Cell‐Mediated Cytotoxicity Against Hepatocellular Carcinoma

Scientists report, that sorafenib acts via direct immune‐modulation indispensable for its anti‐tumor activity. In vivo cell depletion experiments in two orthotopic hepatocellular carcinoma mouse models as well as in vitro analysis identified macrophages (MΦ) as the key mediators of the anti‐tumoral effect and demonstrated a strong interdependency of MΦ and natural killer (NK) cells for efficient tumor cell killing. [Hepatology] Abstract

Transcription Factors IRF8 and PU.1 Are Required for Follicular B Cell Development and BCL6-Driven Germinal Center Responses

Investigators report that double deletion of floxed Irf8 and Spi1 by Mb1-Cre in the B cell lineage resulted in severe defects in the development of follicular and germinal center B cells. [Proc Natl Acad Sci USA] Abstract

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T Cells and the Skin: From Protective Immunity to Inflammatory Skin Disorders

The authors consider how a better understanding of cutaneous T cell responses can aid in the development of effective new therapies for immune-mediated cutaneous diseases. [Nat Rev Immunol] Abstract

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Provectus Biopharmaceuticals Announces Acceptances of PV-10 Poster Presentations

Provectus announced that data from clinical trials of lead investigational cancer agent PV-10 will be presented on two poster presentations. [Press release from Provectus Biopharmaceuticals, Inc. discussing research to be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Mateon and Oncotelic Complete Their Merger and Create a New Immuno-Oncology Company with a Late-Stage Clinical Asset against Cancer and a Promising Product Pipeline

Mateon Therapeutics, Inc. and Oncotelic Inc. announced that they have completed their previously announced merger. The combined company has a focused pipeline of TGF-β RNA Therapeutics for late stage cancers, including gliomas, pancreatic cancer and melanoma. [Mateon Therapeutics, Inc.] Press Release

Orgenesis Announces Collaboration Agreement with Columbia University to Develop Cellular Vaccination Product Platform for Pancreatic, Hepatic and Cholangiocarcinoma Cancers

Orgenesis Inc. announced that it has entered into an agreement with Columbia University, by which it will fund research to develop a cellular vaccination product platform, which it has licensed from Columbia University, for pancreatic, hepatic and cholangiocarcinoma cancers. [Orgenesis Inc.] Press Release

PureTech Health Announces Collaboration with Boehringer Ingelheim to Advance Immuno-Oncology Product Candidates Using Its Lymphatic Targeting Platform

PureTech Health plc announced that it has entered into a research collaboration with Boehringer Ingelheim to develop novel product candidates for an undisclosed number of targets by leveraging PureTech’s proprietary lymphatic targeting technology for immune modulation. [PureTech Health plc] Press Release

Idronoxil Confirmed as New ImmunoOncology Drug

Noxopharm released data from the first series of pre-clinical studies confirming that idronoxil, the active ingredient in the company’s anti-cancer drug candidate, Veyonda^®, activates the immune system. [Noxopharm] Press Release

Viracta Receives Orphan Drug Designation from the US FDA for Its Lead Epigenetic Drug Candidate Nanatinostat for EBV-Associated Cancers

Viracta Therapeutics, Inc. announced that the FDA has granted Orphan Drug Designations to their Phase II drug candidate, nanatinostat, in combination with the antiviral valganciclovir, for the treatment of post-transplant lymphoproliferative disorder, plasmablastic lymphoma, and angioimmunoblastic T cell lymphoma. [Viracta Therapeutics, Inc.] Press Release

FDA Grants Orphan Drug Designation Status to NeoImmuneTech’s Hyleukin-7 for Idiopathic CD4⁺ Lymphocytopenia Treatment

NeoImmuneTech, Inc. announced that the FDA has granted Orphan Drug Designation to Hyleukin-7™, a T cell amplifier, in development for the treatment of idiopathic CD4⁺ lymphocytopenia. [NeoImmuneTech, Inc. (Business Wire, Inc.)] Press Release

US Universities Reassess Collaborations with Foreign Scientists in Wake of NIH Letters

Kuspa’s attempt to stay ahead of NIH came to naught. A few months into the audit, Baylor College of Medicine received letters from the US National Institutes of Health (NIH) asking about four scientists it believed had violated the agency’s rule requiring them to disclose all foreign ties relating to their research. [ScienceInsider] Editorial

Elsevier and Norway Agree on New Open-Access Deal

After unsuccessful negotiations between a coalition of Norwegian organizations and the academic publisher Elsevier culminated in cancelled subscriptions earlier this year, the two have successfully established a new nationwide licensing agreement. [The Scientist] Editorial

Fearing No-Deal Brexit, European Funder Orders UK Researchers to Transfer Grants

The prospect of Brexit, the United Kingdom’s departure from the European Union, has loomed long and large over researchers, but the effects on funding, so far, have been speculative. Now, a European funding agency has made a pre-emptive strike in advance of Brexit, changing a policy that directly impacts grants in the United Kingdom. [ScienceInsider] Editorial

NEW EMBL Conference: Cancer Genomics
November 4-6, 2019
Heidelberg, Germany

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

Senior Staff Scientist – Functional Genomics (Wellcome Sanger Institute)

Postdoctoral Position – Neuro-Immune Interaction/Immunology (KU Leuven)

Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Postdoctoral Fellow – Immuno-Oncology (Georgetown Lombardi Comprehensive Cancer Center)

Faculty Position – Immunology (Fox Chase Cancer Center)

Research Fellow – Protective and Aberrant Immunity (Monash University)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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