Human Immunology News Volume 7.17 | May 7 2019

TOP STORY

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-Cell Transcriptomics and Mass Cytometry

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), researchers applied single-cell RNA sequencing, mass cytometry, bulk RNA sequencing and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis. [Nat Immunol] Abstract

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Akt and STAT5 Mediate Naïve Human CD4⁺ T-Cell Early Metabolic Response to TCR Stimulation

Scientists showed that at rest cultured human effector memory and central memory CD4⁺ T-cells have elevated levels of glycolysis and oxidative phosphorylation, in comparison to naïve T-cells. [Nat Commun] Full Article

Human Interleukin-2 Receptor β Mutations Associated with Defects in Immunity and Peripheral Tolerance

The authors report three homozygous mutations in the interleukin-2 receptor β chain (IL2RB) gene of eight individuals from four consanguineous families that cause disease by distinct mechanisms. Nearly all patients presented with autoantibodies, hypergammaglobulinemia, bowel inflammation, dermatological abnormalities, lymphadenopathy, and cytomegalovirus disease. [J Exp Med] Abstract

A Novel Human IL2RB Mutation Results in T and NK Cell-Driven Immune Dysregulation

Investigators report the first human defect in interleukin (IL)-2Rβ, occurring in two infant siblings with a homozygous IL2RB mutation in the WSXWS motif, manifesting as multisystem autoimmunity and susceptibility to CMV infection. [J Exp Med] Abstract | Press Release | Graphical Abstract

Urban Airborne Particle Exposure Impairs Human Lung and Blood Mycobacterium tuberculosis Immunity

Researchers examined whether in vivo exposure to urban outdoor particulate matter (PM) in Mexico City and in vitro exposure to urban outdoor PM_2.5 alters human host immune cell responses to M. tuberculosis. [Thorax] Abstract

Differential Levels of Regulatory T-Cells and T-Helper-17 Cells in Women with Early and Advanced Endometriosis

The percentages of CD25⁺FOXP3⁺Treg cells within CD4⁺ T cell population was significantly higher in the peritoneal fluid of women with advanced endometriosis than in either early endometriosis or in control women. [J Clin Endocrinol Metab] Abstract

Beta1 Integrin Blockade Overcomes Doxorubicin Resistance in Human T-Cell Acute Lymphoblastic Leukemia

Researchers demonstrated that interactions of human T-cell acute lymphoblastic leukemia cell lines and primary blasts with three-dimensional matrices including Matrigel and collagen type I gel promoted their resistance to doxorubicin via β1 integrin. [Cell Death Dis] Full Article

Distribution of Functional CD4 and CD8 T Cell Subsets in Blood and Rectal Mucosal Tissues

Scientists compared the distribution of T helper (Th) and T cytotoxic (Tc) cell subsets between blood and rectal mucosa (RM) compartments in 62 HIV negative men, focusing primarily on IL-17-producing CD4 and CD8 T cells due to their importance in establishing and maintaining mucosal defenses, and examined associations between the frequencies of Th17 and Tc17 cell subsets and the availability of highly HIV-susceptible target cells in the RM. [Sci Rep] Full Article

A Negative Role for the Interleukin-2-Inducible T-Cell Kinase (ITK) in Human Foxp3⁺ T_REG Differentiation

Using a novel self-delivery siRNA platform, investigators found that ITK knockdown in human primary naïve peripheral blood CD4 T cells increased Foxp3⁺ expression under both regulatory T cell (T_REG) and T helper priming conditions. [PLoS One] Full Article

RNA Sequencing Identifies Clonal Structure of T-Cell Repertoires in Patients with Adult T-Cell Leukemia/Lymphoma

The authors examined the diversity of T-cell receptor clonality and its association with pathogenesis and prognosis in adult T-cell leukemia/lymphoma, a malignancy caused by infection with human T-cell leukemia virus type-1. [npj Genomic Med] Full Article

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New Insights into the Immune Functions of Complement

Scientists consider fundamental mechanisms and novel concepts at the interface of complement biology and immunity and discuss how these affect the maintenance of homeostasis and the development of human pathology. [Nat Rev Immunol] Abstract

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MaxCyte Presents on Manufacturing Process for First CARMA™ Drug Candidate, Including One-Day Cell Processing

MaxCyte announced that Robert Keefe, Director of Technical Operations, provided an oral presentation, titled “Novel mRNA-based Autologous CAR Therapies in Oncology”. [Press release from MaxCyte discussing research presented at the 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Adaptimmune to Present Data Demonstrating that Its Off-the-shelf Process Produces T-Cells from Stem Cells that Respond to Cancer Targets with a SPEAR TCR

Adaptimmune Therapeutics plc presented new and compelling data during an oral presentation about its off-the-shelf SPEAR T-cell program. [Press release from Adaptimmune Therapeutics plc discussing research presented at the 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Brink Biologics Announces Research License Agreement with Worcester Polytechnic Institute for Use of NantKwest’s NK-92^® Cells

Through a limited arrangement, Brink Biologics announced that the company has non-exclusively licensed its next generation bioanalytical testing solution to Worcester Polytechnic Institute. [Brink Biologics, Inc.] Press Release

Tmunity and UC San Francisco Announce Exclusive License and Research Collaboration to Advance TCR T Cell Therapies for Pediatric Cancers

Tmunity Therapeutics, Inc. announced it has entered into an exclusive licensing and research collaboration with the University of California (UC) San Francisco aimed at advancing novel engineered T Cell Receptor (TCR) therapies for rare and currently incurable pediatric conditions with high mortality rates. [Tmunity Therapeutics, Inc.] Press Release

Triumvira Submits Investigational New Drug (IND) Application to the FDA and Clinical Trial Application (CTA) to Health Canada to Evaluate TAC01-CD19, a T Cell Antigen Coupler Therapy, in Ph I/II TACTIC-19 Trial

Triumvira Immunologics Inc. has simultaneously submitted an IND to the FDA and a CTA to Health Canada to initiate a Phase I/II, first-in-human trial of TAC01-CD19, a TAC-T cell therapy product engineered to target CD-19 in patients with relapsed/refractory large B-cell lymphoma. [Triumvira Immunologics Inc. (Business Wire, Inc.)] Press Release

Researchers Ready B Cells for Novel Cell Therapy

Scientists at Seattle Children’s Research Institute are paving the way to use gene-edited B cells – a type of white blood cell in the immune system – to treat a wide range of potential diseases that affect children, including hemophilia and other protein deficiency disorders, autoimmune diseases, and infectious diseases. [Seattle Children’s Research Institute] Press Release

Black Academics Publish One-Fifth of South Africa’s Research

The proportion of scientific articles published by academics in South Africa who are black, colored or of Indian origin has risen almost tenfold since the end of apartheid, to about one-third, finds a report on scholarly publishing in the country. [Nature News] Editorial

White House to Convene Committee to Address Research Obstacles

The leaders of the White House Office of Science and Technology, National Institutes of Health, National Science Foundation, National Institute of Standards and Technology, and the Department of Energy’s science division have formed a committee “to address issues facing the US research community,” President Donald Trump’s administration announced. [The Scientist] Editorial

NEW Advanced Cell Therapies and Tissue Engineering
November 14-16, 2019
Milan, Italy

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NEW Postdoctoral Scientist – Cancer Immunotherapy (Peter MacCallum Cancer Centre)

NEW Postdoctoral Position – Immunology (KU Leuven)

NEW Professor – Basal Allergy and Immunology (Aarhus University)

Postdoctoral Opportunities – Tumor Microenvironment/Immunology (Oregon Health & Science University)

Postdoctoral Research Fellow – Mucosal Immunology and the Microbiome (Massachusetts General Hospital)

Postdoctoral Research Fellow – Immunology and Bioengineering (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Postdoctoral Associate – Cancer Biology/Tumor Immunology (Weill Cornell Medicine)

Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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