Human Immunology News Volume 6.17 | May 1 2018

TOP STORY

Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses

To expand the capability of chimeric antigen receptor (CAR) T cells, scientists present a split, universal, and programmable CAR system that simultaneously encompasses multiple critical “upgrades,” such as the ability to switch targets without re-engineering the T cells, finely tune T cell activation strength, and sense and logically respond to multiple antigens. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Transcript-Indexed ATAC-Seq for Precision Immune Profiling

The authors combined sequencing of the T cell receptor (TCR)-encoding genes with an assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on TCR specificity and epigenomic state of individual T cells. [Nat Med] Abstract

Determinants of Response and Resistance to CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy of Chronic Lymphocytic Leukemia

Transcriptomic profiling revealed that CAR T cells from complete-responding patients with chronic lymphocytic leukemia were enriched in memory-related genes, including IL-6/STAT3 signatures, whereas T cells from non-responders upregulated programs involved in effector differentiation, glycolysis, exhaustion and apoptosis. [Nat Med] Abstract | Press Release

Alloreactive Fetal T Cells Promote Uterine Contractility in Preterm Labor via IFN-γ and TNF-α

To examine the fetal immune system in the relevant clinical setting, scientists analyzed maternal and cord blood in patients with preterm labor and healthy term controls. They report that the cord blood of preterm infants has higher amounts of inflammatory cytokines and a greater activation of dendritic cells. [Sci Transl Med] Abstract

Widespread Intronic Polyadenylation Diversifies Immune Cell Transcriptomes

The authors analyzed 46 3ʹ-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma samples and created an atlas of 4927 high-confidence intronic polyadenylation events represented in these cell types. [Nat Commun] Full Article

IL-21 Drives Expansion and Plasma Cell Differentiation of Autoreactive CD11c^hiT-bet⁺ B Cells in SLE

Investigators showed that an unusual CD11c^hiT-bet⁺ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in systemic lupus erythematosus (SLE) patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. [Nat Commun] Full Article

A Screen of Crohn’s Disease-Associated Microbial Metabolites Identifies Ascorbate as a Novel Metabolic Inhibitor of Activated Human T Cells

Researchers screened 139 predicted Crohn’s disease-associated microbial metabolites for their bioactivity on human CD4⁺ T-cell functions induced by disease-associated T helper 17 polarizing conditions. [Mucosal Immunol] Abstract

A Defect in KCa3.1 Channel Activity Limits the Ability of CD8⁺ T Cells from Cancer Patients to Infiltrate an Adenosine-Rich Microenvironment

Investigators conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8⁺ T cells from head and neck squamous cell carcinoma (HNSCC) patients. The chemotaxis of HNSCC CD8⁺ T cells was reduced in the presence of adenosine, and the effect was greater on HNSCC CD8⁺ T cells than on healthy donor CD8⁺ T cells. [Sci Signal] Abstract

Long Non-Coding RNA Lnc-Tim3 Exacerbates CD8 T Cell Exhaustion via Binding to Tim-3 and Inducing Nuclear Translocation of Bat3 in HCC

Researchers showed that Lnc-Tim3 is upregulated and negatively correlates with IFN-γ and IL-2 production in tumor-infiltrating CD8 T cells of hepatocellular carcinoma (HCC) patients. [Cell Death Dis] Full Article

Feraheme^® Suppresses Immune Function of Human T Lymphocytes through Mitochondrial Damage and MitoROS Production

The authors conducted a mechanistic investigation using an injectable form of iron oxide nanoparticle, Feraheme^®. In the cultures of primary human T cells, Feraheme induced miotochondrial oxidative stress and resulted in changes in mitochondrial dynamics, architecture, and membrane potential. [Toxicol Appl Pharmacol] Abstract

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Recasting Human Vδ1 Lymphocytes in an Adaptive Role

Vδ1 T cells are the predominant tissue-associated γδ T cell subset in humans, and can recognize signs of cellular dysregulation, including viral infection and transformation. They are often assumed to be innate-like effectors. [Trends Immunol] Full Article

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STEMCELL Technologies Announces $45 Million Government Funding for Advanced Manufacturing Facility

STEMCELL Technologies announced a $45 million joint funding agreement between the Governments of Canada and British Columbia to help the company build a state-of-the-art advanced manufacturing facility. [STEMCELL Technologies Inc.] Press Release

Sarah Cannon Development Innovations Collaborates with Pivotal on Immuno-Oncology Trials

Sarah Cannon Development Innovations announced a new strategic collaboration with Pivotal to expand access to novel immunotherapies in early phase clinical trials in Europe. [Sarah Cannon] Press Release

Gilead and Verily Announce Scientific Collaboration to Identify and Understand Immunological and Molecular Drivers of Inflammatory Diseases

Gilead Sciences, Inc. and Verily Life Sciences LLC announced a scientific collaboration using Verily’s Immunoscape platform to identify and better understand the immunological basis of three common and serious inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and lupus-related diseases. [Gilead Sciences, Inc.] Press Release

Science in North Korea: How Easing the Nuclear Stand-Off Might Bolster Research

The isolated nation publishes fewer than 100 scholarly articles a year — but as political tensions thaw, researchers hope for greater collaboration. [Nature News] Editorial

Federal Appeals Court Hears CRISPR Patent Dispute

A federal appeals court heard arguments that the U.S. patent office made legal mistakes when reviewing its ruling on CRISPR, the genome editor. [ScienceInsider] Editorial

Harassment and Discrimination Allegations Roil a Top US Biomedical Institute

Allegations of sexual harassment and assault levelled against Inder Verma, a prominent cancer biologist at the Salk Institute for Biological Studies in La Jolla, California, cap a tumultuous ten months for the well-known research centre. [Nature News] Editorial

NEW Cell Symposia: Translational Immunometabolism
June 24-26, 2018
Basel, Switzerland

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NEW Postdoctoral Researcher Positions – Rapid Identification of Autoantigens in Autoimmune Disease (BioMed X Innovation Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

PhD Student – Immunology of Cell Death & Cancer Immunotherapy (KU Leuven)

Scientist/Senior Scientist – Lentivirus Production (Obsidian Therapeutics)

Scientist/Senior Scientist – Bioinformatics and Data Sciences (Obsidian Therapeutics)

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

Research Scientist – Biomarker Development (Kymab)

Postdoctoral Position – Onco-ImmunoMetabolism (San Raffaele Scientific Institute)

Assistant/Associate Professor – Immunology (Saint Louis University)

Scientist – Immune Tolerance (Moderna Therapeutics)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

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