Immune Regulation News Volume 9.14 | Apr 21 2017

TOP STORY

Seemingly Innocuous Virus Can Trigger Celiac Disease

Infection with reovirus, a common but otherwise harmless virus, can trigger the immune system response to gluten that leads to celiac disease. The study further implicates viruses in the development of autoimmune disorders such as celiac disease and type 1 diabetes, and raises the possibility that vaccines could one day be used to prevent these diseases. [Press release from the University of Chicago discussing online prepublication in Science] Press Release | Abstract

(Ranked by impact factor of the journal)

Landscape of Immunogenic Tumor Antigens in Successful Immunotherapy of Virally Induced Epithelial Cancer

Scientists used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. [Science] Abstract

Glutathione Primes T Cell Metabolism for Inflammation

Researchers report that glutathione (GSH) is essential for T cell effector functions through its regulation of metabolic activity. Conditional gene targeting of the catalytic subunit of glutamate cysteine ligase blocked GSH production specifically in murine T cells. [Immunity] Abstract | Press Release | Graphical Abstract

Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8⁺ T Cell Terminal Differentiation and Loss of Multipotency

The authors profiled active and repressed (H3K27me3) chromatin in naive, memory precursor (MP), and terminally differentiated effector (TE) CD8⁺ T cells during viral infection revealed increased H3K27me3 deposition at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency. [Immunity] Abstract | Graphical Abstract

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

Scientists demonstrated that CD25 expression is largely restricted to tumor-infiltrating regulatory T (Treg) cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. [Immunity] Abstract | Graphical Abstract

Monocytic and Granulocytic Myeloid Derived Suppressor Cells Differentially Regulate Spatiotemporal Tumor Plasticity during Metastatic Cascade

Investigators demonstrated that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumor and distant organs with different time kinetics and regulate spatiotemporal tumor plasticity. They provide evidence that tumor-infiltrated mMDSCs facilitate tumor cell dissemination from the primary site by inducing EMT/CSC phenotype. [Nat Commun] Full Article | Press Release

Transiently Antigen-Primed B Cells Return to Naive-Like State in Absence of T-Cell Help

Researchers showed that in the presence of T-cell help, single transient antigen acquisition is sufficient to recruit B cells into the germinal center and induce memory and plasma cell responses. [Nat Commun] Full Article

IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

Scientists showed that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet. Their results showed that IGF1 signaling shapes the macrophage-activation phenotype. [Cell Rep] Full Article | Graphical Abstract

Liver Receptor Homolog-1 (NR5a2) Regulates CD95/Fas Ligand Transcription and Associated T-Cell Effector Functions

CD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis factor family with important functions in the regulation of T-cell homeostasis and cytotoxicity. The authors report that liver receptor homolog-1 (LRH-1) was expressed in primary and secondary lymphatic tissues, as well as in CD4⁺ and CD8⁺ T cells. LRH-1 directly binds to its binding sites in the FASLG promoter, and thereby drives FASLG promoter activity. [Cell Death Dis] Full Article

Characterization of C-Maf⁺Foxp3⁻ Regulatory T Cells Induced by Repeated Stimulation of Antigen-Presenting B Cells

Investigators showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator as well as cytotoxic T-lymphocyte-associated protein 4 after repeated stimulation of B cells in a cell-cell contact-dependent manner. [Sci Rep] Full Article

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Crosstalk between the Secretory and Autophagy Pathways Regulates Autophagosome Formation

The authors discuss recent findings that have begun to uncover how different parts of the secretory pathway directly and indirectly contribute to autophagosome formation during starvation. [Dev Cell] Abstract

Viewing Immune Regulation as It Happens—In Vivo Imaging for Investigation of Regulatory T Cell Function

Scientists describe the studies that have utilized multiphoton microscopy to examine Regulatory T cells (Treg) behavior in vivo. These studies have investigated Treg behavior in lymph nodes and spleen, as well as in peripheral organs such as skin, small intestine and bone marrow. [Immunol Cell Biol] Abstract

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

Novartis CAR-T Cell Therapy CTL019 Receives FDA Breakthrough Therapy Designation for Treatment of Adult Patients with r/r DLBCL

Novartis announced that the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL), who have failed two or more prior therapies. [Novartis AG] Press Release

The Human Vaccines Project, Vanderbilt and Illumina Join Forces to Decode the Human Immunome

The Human Vaccines Project and Vanderbilt University Medical Center announced that they joined forces with Illumina, Inc. to decipher the human immunome, the genetic underpinnings of the immune system. Illumina will provide the genetic sequencing technologies and expertise required to process the massive amounts of data required to decode the human immunome. [The Human Vaccines Project (PR Newswire Association, LLC.)] Press Release

NYU Langone Research Leads to Accelerated Approval of Bladder Cancer Immunotherapy Drug

Findings from a clinical trial led by a researcher at NYU Langone’s Perlmutter Cancer Center helped pave the way for the recent, accelerated approval by the United States Food and Drug Administration of a highly effective immunotherapy as a first-line treatment for patients with advanced bladder cancer who are not eligible for treatment with standard chemotherapy. The drug, atezolizumab, marketed as Tecentriq^® and part of a class of drugs known as checkpoint inhibitors, was found to shrink bladder tumors by at least 30 percent and stall new tumor growth in 28 of 119 patients (24 percent). [NYU Langone’s Perlmutter Cancer Center] Press Release

Power Struggle Erupts at Utah Cancer Institute over Director’s Firing

The abrupt dismissal of the head of a Utah cancer center is causing backlash from its faculty—and its major philanthropic funder—in a struggle over the center’s autonomy from the University of Utah in Salt Lake City. And nearly 2000 researchers have signed a petition calling on the university to reverse its decision. [ScienceInsider] Editorial

For Congress, March for Science is a Democratic Event

Organizers of the March for Science have deliberately avoided reaching out to U.S. elected officials, saying that they want the rallies to be apolitical. As a result, few members of Congress will be participating in the main event in Washington, D.C., and at hundreds of satellite marches across the country. [ScienceInsider] Editorial

NEW ISSCR Annual Meeting 2017
June 14-17, 2017
Boston, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Anderson Faculty (Wellcome Trust Sanger Institute)

NEW Postdoctoral Associate Position – Immunometabolism and Myeloid Cell Regulation within the Tumor Microenvironment (University of Louisville)

NEW Postdoctoral Fellow(s) – Histocompatibility Antigen-Specific T Cells (University of Pittsburgh)

NEW Senior Research Scientist – Natural Killer Cell Therapy (Anthony Nolan)

Postdoctoral Scientist – Innate Immune Biology in Cirrhosis (The Foundation for Liver Research)

Research Assistant – Immunology (University of Cambridge)

Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Postdoctoral Positions – Computational Biology (The University of Texas MD Anderson Cancer Center)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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