Human Immunology News Volume 5.39 | Oct 3 2017

TOP STORY

COPD Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in NSCLC

Scientists aimed to profile the immune cell composition and function in patients with non-small cell lung cancer (NSCLC) and describe the effect of chronic obstructive pulmonary disease (COPD) on lung and tumor microenvironments. They observed an increased numbers of lymphocytes in the lungs of patients with COPD, consisting of increased IFN producing CD8⁺ and CD4⁺ lymphocytes. [Am J Respir Crit Care Med] Abstract

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Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells were presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. [Cell Rep] Full Article | Graphical Abstract

Prostaglandin E2 Leads to the Acquisition of DNMT3A-Dependent Tolerogenic Functions in Human Myeloid-Derived Suppressor Cells

Comparison of myeloid-derived suppressor cell (MDSC) and dendritic cell DNA methylomes revealed extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A levels. [Cell Rep] Full Article | Graphical Abstract

Toll-Like Receptor-Mediated Upregulation of CXCL16 in Psoriasis Orchestrates Neutrophil Activation

CXCL16 potently induced migration of neutrophils and enhanced the chemotactic effect of IL-8. The positive feedback loop was supported by IL-8 enhancing CXCL16 production of neutrophils. [J Invest Dermatol] Abstract

H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3

Investigators studied changes to promoter H3K27me3 during activation of human naive and memory CD4 T cells. They showed that these changes occur relatively early after activation of naive and memory cells and that demethylation is the predominant change to H3K27me3 at this time point, reinforcing high expression of target genes. [J Immunol] Abstract

Cytokine-Induced Autophagy Promotes Long-Term VCAM-1 but not ICAM-1 Expression by Degrading Late-Phase IκBα

Researchers hypothesized that autophagy facilitates expression of endothelial adhesion molecules. TNFα and IL-1β induced autophagy markers in human umbilical vein endothelial cells and inhibition of autophagy by 3-methyladenine blocked adhesion of Jurkat lymphocytes. [Sci Rep] Full Article

Lys63-Polyubiquitination by the E3 Ligase Casitas B-Lineage Lymphoma-b (Cbl-b) Modulates Peripheral Regulatory T Cell Tolerance in Patients with Systemic Lupus Erythematosus

Scientists found a defective Cbl-b expression in regulatory T cells from lupus patients in contrast to healthy controls, which was related with resistance to suppression. This feature was associated with deficient K63 polyubiquitination substrates and enhanced expression of phosphorylated STAT3 in regulatory T cells from lupus patients. [Clin Exp Immunol] Abstract

Effects of Rituximab and Dexamethasone on Regulatory and Pro-Inflammatory B-Cell Subsets in Patients with Primary Immune Thrombocytopenia

Researchers investigated the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia before and 12 months after treatment with rituximab + dexamethasone or dexamethasone. [Eur J Haematol] Abstract

Expression of CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells, Interleukin 10 and Transforming Growth Factor β in Newly Diagnosed Type 2 Diabetic Patients

To examine potential relationships among regulatory T cells (Tregs), insulin resistance, blood lipid content, and related cytokines, scientists investigated the frequency of CD4⁺CD25⁺Foxp3⁺ Tregs, as well as expression levels of interleukin 10 and transforming growth factor-β in newly diagnosed type 2 diabetes mellitus patients. [Exp Clin Endocrinol Diabetes] Abstract

Dynamics of the Human Antibody Repertoire after B Cell Depletion in Systemic Sclerosis

The authors found systemic sclerosis with pulmonary arterial hypertension to be associated with anomalies in B cell development, namely, altered VDJ rearrangement frequencies and an increased somatic mutation–fixation probability in expanded B cell lineages. [Sci Immunol] Full Article

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The Spectrum of T Cell Metabolism in Health and Disease

The authors introduce the idea that the spectrum of immune cell metabolic states can provide a basis for categorizing human diseases. They summarize the metabolic and interlinked signaling requirements of T cells responding to acute infection. They then discuss how metabolic reprogramming of T cells is linked to disease. [Nat Rev Immunol] Abstract

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Casebia Therapeutics Announces License and Collaboration Agreements with Seattle Children’s Research Institute

Casebia Therapeutics and Seattle Children’s Research Institute announced an exclusive license agreement and research collaboration to explore new methods to treat and prevent autoimmune disease using CRISPR/Cas9 gene-edited regulatory T cells. [Casebia Therapeutics] Press Release

NCI Renews Lymphoma Immunotherapy Research Grant

The Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital has received an $11.5 million, five-year renewal grant from the National Cancer Institute to continue advancing translational lymphoma research by developing and testing new forms of T-cell immunotherapies to fight the disease. [Baylor College of Medicine] Press Release

OSE Immunotherapeutics Signs a License Option Agreement with Inserm to Develop a New Cancer Immunotherapy Targeting Myeloid Cells

OSE Immunotherapeutics SA announced that the company has entered into an agreement with Inserm Transfert, on behalf of Inserm and Nantes University, to collaborate on the development of a cancer immunotherapy targeting a new suppressive myeloid cell receptor. [OSE Immunotherapeutics SA] Press Release

NantKwest Announces Successful First in Human Administration of CD16 High Affinity Natural Killer (haNK) Cells

NantKwest Inc. announced the clinical implementation of the company’s haNK cell therapy program to human clinical trials with the first participants treated in the first-in-human, Phase I haNK cell therapy clinical trial targeting a wide range of cancer types. [NantKwest Inc.] Press Release

After Upheaval, Russian Academy of Sciences Gets New Leader

After months of uncertainty, the Russian Academy of Sciences finally has a new leader. Russian President Vladimir Putin approved physicist Alexander Sergeyev as the academy’s president for the next five years. Sergeyev has vowed to secure more money for Russian science and create a fund, through a new tax on fossil fuel company profits, for upgrading the country’s antiquated research infrastructure. [ScienceInsider] Editorial

Researchers Caught in Growing Rift over Catalan Independence

Scientists in Catalonia are feeling the ripples of a severe crisis as the region’s bid for independence from Spain comes to a head. [ScienceInsider] Editorial

French Government Proposes Big Science-Spending Boost

French research funding is set for a heartening increase in the country’s first budget under President Emmanuel Macron, if draft 2018 plans are voted into law. [Nature News] Editorial

NEW Keystone Symposia: Aging, Inflammation and Immunity
February 25-March 1, 2018
Austin, Texas, United States

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NEW Postdoctoral Researcher – Immunology (University of Luxembourg)

NEW Postdoctoral Fellowship – Tumor Immunology (UT Southwestern Medical Center)

NEW Full Professorship/Group Leader/Assistant Professor Positions – Systems Immunology (Julius Maximilians University of Würzburg)

NEW Postdoctoral Training Fellow – Immune Mechanisms (The Francis Crick Institute)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (University of Rochester Medical Center)

Research Scientist – Immuno-oncology (Kymab Ltd.)

Postdoctoral Researcher – Development of Immune System (Lund University)

Postdoctoral Fellow – Immunology Cell Based Assay (Turnstone Biologics Inc.)

Postdoctoral Fellow – Immunology Relating to Type 1 Diabetes (Icahn School of Medicine at Mount Sinai)

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

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