Immune Regulation News Volume 9.42 | Nov 3 2017

TOP STORY

Your Gut Bacteria Could Determine How You Respond to Cutting-Edge Cancer Drugs

Two teams offer a raft of evidence from cancer patients suggesting that the gut microbiome—the community of bacteria, viruses, and other bugs living in our digestive tracts—helps determine whether tumors shrink when treated with immunotherapy drugs. [Editorial from ScienceInsider discussing online prepublications in Science] Editorial | Abstract 1 | Abstract 2 | Press Release 1 | Press Release 2

(Ranked by impact factor of the journal)

Reversing SKI–SMAD4-Mediated Suppression Is Essential for T_H17 Cell Differentiation

Scientists revealed that transforming growth factor β (TGFβ) enables T helper 17 (T_H17) cell differentiation by reversing SKI–SMAD4-mediated suppression of the expression of the retinoic acid receptor-related orphan receptor γt (RORγt). They found that, unlike wild-type T cells, SMAD4-deficient T cells differentiate into T_H17 cells in the absence of TGFβ signaling in a RORγt-dependent manner. [Nature] Abstract

Oxidative Stress Controls Regulatory T Cell Apoptosis and Suppressor Activity and PD-L1-Blockade Resistance in Tumor

Live T_reg cells suppress antitumor immunity, but how T_reg cells behave in the metabolically abnormal tumor microenvironment remains unknown. The authors showed that tumor T_reg cells undergo apoptosis, and such apoptotic T_reg cells abolish spontaneous and PD-L1-blockade-mediated antitumor T cell immunity. [Nat Immunol] Abstract | Press Release

Kenny Mediates Selective Autophagic Degradation of the IKK Complex to Control Innate Immune Responses

Researchers showed that Drosophila Kenny, the homolog of mammalian IKKγ, is a selective autophagy receptor that mediates the degradation of the IκB kinase complex. Selective autophagic degradation of the IκB kinase complex prevented constitutive activation of the immune deficiency pathway in response to commensal microbiota. [Nat Commun] Full Article

Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice

Scientists found that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for liver tolerance in concanavalin A-induced acute liver injury. Gut-derived IL-22 enhanced mucosal barrier function and promoted the recruitment of regulatory cDCs to the liver. [Cell Rep] Full Article | Graphical Abstract

B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells

The authors showed that CD28 signaling is required for follicular regulatory T (T_FR) cell differentiation. Treg-specific deletion of CD28 caused a reduction in T_FR cell numbers and function, which resulted in increased germinal center B cells and Ab production. [J Immunol] Abstract

Palmitate Inhibits Arthritis by Inducing t–bet and gata–3 mRNA Degradation in iNKT Cells via IRE1α-Dependent Decay

Investigators report an inhibitory effect of saturated long chain fatty acids (LCFAs) on transcription factors in invariant natural killer T (iNKT) cells. Among the saturated LCFAs, palmitic acid specifically inhibited IL-4 and IFN-γ production and reduced gata–3 and t–bet transcript levels in iNKT cells during TCR-mediated activation. [Sci Rep] Full Article

Anti-Inflammatory and Anti-Fibrotic Effects of Intravenous Adipose-Derived Stem Cell Transplantation in a Mouse Model of Bleomycin-Induced Interstitial Pneumonia

The authors investigated the therapeutic effect of intravenous adipose-derived stem cell (AdSC) transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner. [Sci Rep] Full Article

Induction of Porcine-Specific Regulatory T Cells with High Specificity and Expression of IL-10 and TGF-β1 Using Baboon-Derived Tolerogenic Dendritic Cells

A fast three-day method to generate baboon-derived tolerogenic dendritic cells is provided that allows subsequent induction of porcine-specific Treg displaying high porcine-antigen specificity and expression of IL-10 and TGF-β1. [Xenotransplantation] Full Article

Microbiota Control Immune Regulation in Humanized Mice

Researchers studied how the microbiome affects regulation of human immune cells in humanized mice. When humanized mice were treated with a cocktail of four antibiotics, there was an increase in the frequency of effector T cells in the gut wall, circulating levels of IFN-γ, and appearance of anti-nuclear antibodies. [JCI Insight] Full Article

Human Regulatory T Cells Undergo Self-Inflicted Damage via Granzyme Pathways upon Activation

Investigators describe a new mechanism of Treg self-inflicted damage. They showed that granzymes A and -B, which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells. [JCI Insight] Full Article

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Therapeutic Application of T Regulatory Cells in Composite Tissue Allotransplantation

The authors focus on a dominant form of Treg cells expressing CD4⁺CD25⁺ surface molecules and a forkhead box P3 transcription factor with immune tolerant and immune homeostasis activities. [J Transl Med] Full Article

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

Rgenix Reports Preliminary Phase Ia/b Clinical Data Demonstrating Immune-Stimulatory Activity with RGX-104 in Advanced Cancer Patients

Rgenix, Inc. announced preliminary data from an ongoing Phase Ia/b clinical trial with its lead oral investigational agent, RGX-104. [Press release from Rgenix, Inc. (Business Wire, Inc.) discussing research presented at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Philadelphia] Press Release

Janssen to Present 40 Abstracts, including 8 Oral Presentations, with New Data on DARZALEX^® (Daratumumab), IMBRUVICA^® (Ibrutinib) and Other Compounds from Robust Portfolio

New data for the immunotherapy DARZALEX^® and first-in-class BTK inhibitor IMBRUVICA^® are among eight oral presentations to be featured. [Press release from Janssen Research & Development, LLC discussing research to be presented at the 59^th American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Bioniz Therapeutics to Present New Data

Bioniz Therapeutics, Inc. announced that new data from the company’s lead BNZ-1 program will be presented. [Press release from Bioniz Therapeutics, Inc. (PR Newswire Association LLC.) discussing research to be presented at the 59^th American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

First Clinical Data from Combination of X4P-001-IO and Keytruda^® (Pembrolizumab) in Patients with Melanoma Will Be Presented

X4 Pharmaceuticals announced that the first data from its ongoing Phase Ib clinical study of X4P-001-IO in patients with melanoma will be presented. [Press release from X4 Pharmaceuticals discussing research to be presented at the 2017 Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

Compugen to Enter Research Collaboration with Mount Sinai on Novel Myeloid Immuno-Oncology Targets

Compugen Ltd. announced the initiation of a multi-year cancer immunotherapy research collaboration with Mount Sinai, under the direction of Miriam Merad, MD, PhD, Director of the Precision Immunology Institute and Co-Leader of the Cancer Immunology program and Mount Sinai Professor in Cancer Immunology at the Icahn School of Medicine at Mount Sinai in New York. [Compugen Ltd.] Press Release

The First Patient Enrolled in the ReITIrate Study Evaluating Immune Tolerance Induction with Elocta^®

Swedish Orphan Biovitrum AB announced that the first patient has been enrolled in the open-label, multicenter ReITIrate study. The ReITIrate study is designed to investigate the immune tolerance induction potential of Elocta^® in patients with hemophilia A who have developed inhibitors which have failed to be resolved with other therapies. [Swedish Orphan Biovitrum AB] Press Release

U.S. Oversight of Risky Pathogen Research Has Flaws, Report Finds

The program that keeps watch over the management of dangerous pathogens at research laboratories still isn’t up to snuff, according to a new report from the U.S. Government Accountability Office. [ScienceInsider] Editorial

Leading Western Publisher Bows to Chinese Censorship

Springer Nature, whose publications include Nature and Scientific American, acknowledged that at the government’s request, it had removed articles from its mainland site that touch on topics the ruling Communist Party considers sensitive, including Taiwan, Tibet, human rights and elite politics. [The New York Times] Editorial

House Science Chair to Retire from Congress

The controversial chairperson of the science committee in the U.S. House of Representatives announced that he will not seek re-election to Congress next fall. The pending departure of Representative Lamar Smith could give the U.S. scientific community a chance to recalibrate a rocky five-year relationship with a key congressional committee. [ScienceInsider] Editorial

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