Immune Regulation News Volume 9.33 | Sep 1 2017

TOP STORY

Finding What Fuels the “Runaway Train” of Autoimmune Diseases

Scientists revealed that rogue B cells can trigger an “override” that launches the body into an autoimmune attack. [Press release from Boston Children’s Hospital discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

IFN-λ Suppresses Intestinal Inflammation by Non-Translational Regulation of Neutrophil Function

Researchers report that neutrophils responded to interferon-λ (IFN-λ). They found that in addition to inducing interferon-stimulated genes transcription, IFN-λ (but not IFN-β) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils. [Nat Immunol] Abstract

Proteasome Activity Regulates CD8⁺ T Lymphocyte Metabolism and Fate Specification

During an immune response, CD8⁺ T lymphocytes can undergo asymmetric division, giving rise to daughter cells that exhibit distinct tendencies to adopt terminal effector and memory cell fates. Scientists showed that “pre-effector” and “pre-memory” cells resulting from the first CD8⁺ T cell division in vivo exhibited low and high rates of endogenous proteasome activity, respectively. [J Clin Invest] Full Article | Press Release

Interactions between Fibroblastic Reticular Cells and B Cells Promote Mesenteric Lymph Node Lymphangiogenesis

The authors demonstrated a crucial role for lymphotoxin-beta receptor signaling to fibroblastic reticular cells by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. [Nat Commun] Full Article

Hit-And-Run Programming of Therapeutic Cytoreagents Using mRNA Nanocarriers

Scientists demonstrated that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells. They imprinted a long-lived phenotype exhibiting improved antitumor activities into T-cells by transfecting them with mRNAs that encode a key transcription factor of memory formation. [Nat Commun] Full Article | Press Release

Interferon-Gamma Regulates Inflammatory Cell Death by Targeting Necroptosis in Experimental Autoimmune Arthritis

Scientists hypothesized that interferon γ (IFN-γ) would reduce inflammatory cell death in vitro and that loss of IFN-γ would aggravate inflammation in vivo. IFN-γ downregulated necroptosis and the expression of cellular FLICE-like inhibitory protein and mixed lineage kinase domain-like. [Sci Rep] Full Article

Immune Activated Monocyte Exosomes Alter MicroRNAs in Brain Endothelial Cells and Initiate an Inflammatory Response through the TLR4/MyD88 Pathway

The authors showed that monocytes activated by interferon alpha, lipopolysaccharide or a combination of both generate exosomes carrying significantly altered microRNA profiles compared to non-activated monocytes. [Sci Rep] Full Article

Role of Lymphocyte Subsets in the Immune Response to Primary B Cell–Derived Exosomes

Scientists investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell–mediated response to B cell–derived exosomes. [J Immunol] Abstract | Press Release

CTLA-4/CD80 Pathway Regulates T Cell Infiltration into Pancreatic Cancer

Using clinically relevant genetic models of pancreatic ductal adenocarcinoma, researchers found that regulatory T cells (Tregs), which constitutively express CTLA-4, accumulate early during tumor development but are largely confined to peritumoral lymph nodes during disease progression. Tregs were observed to regulate CD4⁺, but not CD8⁺, T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. [Cancer Immunol Immunother] Abstract

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Chimeric Antigen Receptor T-Cell Therapies for Lymphoma

The authors review the clinical efficacy and toxicity of chimeric antigen receptor (CAR)-T-cell therapies for lymphoma, and discuss their limitations and future directions with regard to toxicity management, CAR designs and CAR-T-cell phenotypes, conditioning regimens, and combination therapies. [Nat Rev Clin Oncol] Abstract

Natural Killer Cells: Angels and Devils for Immunotherapy

Scientists discuss various parameters to help improve current strategies using natural killer (NK) cells in cancer therapy. Moreover, the chimeric antigen receptor modification, which has revolutionized the concept of immunotherapy, is discussed in the context of NK cells. Lastly, the dark side of NK cells and their involvement in inflammation will also be discussed. [Int J Mol Sci] Full Article | Grapical Abstract

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

New and Updated Data for KEYTRUDA^® (pembrolizumab) from Merck’s Extensive Immuno-Oncology Program to be Presented

Merck announced that studies involving KEYTRUDA^®, the company’s anti-PD-1 therapy, in 12 different types of cancer will be presented. [Press release from Merck discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Novartis Receives First Ever FDA Approval for a CAR-T Cell Therapy, Kymriah^™ (CTL019), for Children and Young Adults with B-Cell ALL that Is Refractory or Has Relapsed at Least Twice

Novartis announced that the US Food and Drug Administration (FDA) has approved Kymriah^™ suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. [Novartis AG] Press Release

State’s Stem Cell Agency Awards $18.2 Million Grant for B Cell Cancer Clinical Trial

The Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine unanimously approved an $18.29 million grant to University of California San Diego School of Medicine researchers to fund a Phase Ib/IIa clinical trial of a novel combination drug therapy for B-cell cancers. [University of California San Diego School of Medicine] Press Release

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

The FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

Science Suffers as China’s Internet Censors Plug Holes in Great Firewall

China is tightening the screws on internet access, again. The latest crackdown—an evolving effort to ban virtual private networks not under government control—could seriously erode scientists’ ability to stay connected with peers abroad. [ScienceInsider] Editorial

NEW Keystone Symposia: Lymphocytes and Their Roles in Cancer
February 11-15, 2018
Keystone, Colorado, United States

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

NEW Assistant Professor – Protective Immunity (Children’s Hospital of Philadelphia)

Postdoctoral Research Associate – Mega Proteins to Control T Cell Signaling (University of Oxford)

Postdoctoral Training Fellows – Cell Death & Inflammation (Institute of Cancer Research)

Postdoctoral Fellowship – Immunology (University of Georgia)

Postdoctoral Research Fellows – Systems Immunology (University of Oslo)

Postdoctoral Scholar – Regulation of Immune Responses (University of Iowa)

Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

Research Fellow Position – Immunology Research (ShanghaiTech University)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte Ltd.)

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

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Principal Senior Scientist – Human Disease Immune Profiling/Precision Immunology (Sanofi)

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

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