Human Immunology News Volume 8.05 | Feb 11 2020

TOP STORY

Single-Cell Transcriptome Analysis of Human Skin Identifies Novel Fibroblast Subpopulation and Enrichment of Immune Subsets in Atopic Dermatitis

Scientists constructed a detailed, high-resolution atlas of cell populations, and assessed variability in cell composition and cell-specific gene expression in the skin of atopic dermatitis (AD) patients versus controls. They performed single-cell RNA-sequencing on skin biopsies from five patients with AD and seven healthy control subjects, using 10x Genomics. [J Allergy Clin Immunol] Abstract | Graphical Abstract

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Epigenetic Driver Mutations in ARID1A Shape Cancer Immune Phenotype and Immunotherapy

Researchers demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to interferon (IFN) responsive genes, caused impaired IFN-gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies as well as in murine cancer models. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Immunological History Governs Human Stem Cell Memory CD4 Heterogeneity via the Wnt Signaling Pathway

Using single cells RNA sequencing and high-dimensional flow cytometry, investigators demonstrated that stem cell memory T lymphocyte (T_SCM) heterogeneity resulted from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 T_SCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. [Nat Commun] Full Article

Sexual-Dimorphism in Human Immune System Aging

The authors characterized peripheral blood mononuclear cells from 172 healthy adults 22-93 years of age using ATAC-seq, RNA-seq, and flow cytometry. These data revealed a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte and cytotoxic cell functions. [Nat Commun] Full Article

Human FC Receptor-Like 3 Inhibits Regulatory T Cell Function and Binds Secretory IgA

Researchers discovered that human Fc receptor-like 3 (FCRL3) stimulation of regulatory T cells inhibited their suppressive function. Moreover, FCRL3 stimulation induced IL-17, IL-26, and IFNγ production and promoted expression of the Th17-defining transcription factor RORγt without affecting FOXP3 expression. They suggest that FCRL3 engagement mediated a transition of regulatory T cells to a pro-inflammatory Th17-like phenotype. [Cell Rep] Full Article | Graphical Abstract

Association of Occupational Exposures with Ex Vivo Functional Immune Response in Workers Handling Carbon Nanotubes and Nanofibers

Whole blood collected from each participant was incubated for 18 hours with and without two microbial stimulants using TruCulture technology to evaluate immune cell activity. Following incubation, supernatants were preserved and analyzed for protein concentrations. [Nanotoxicology] Abstract

Activation of Siglec-7 Results in Inhibition of In Vitro and In Vivo Growth of Human Mast Cell Leukemia Cells

Investigators showed that the inhibitory receptor Siglec-7 was expressed by primary neoplastic mast cells in patients with systemic mastocytosis and by mast cell leukemia cell lines. Activation of Siglec-7 by anti-Siglec-7 monoclonal antibody caused phosphorylation of Src homology region 2 domain-containing phosphatase-1, reduced phosphorylation of KIT and induced growth inhibition in mast cell lines. [Pharmacol Res] Abstract | Graphical Abstract

Cell Death Induced by Dorsomorphin in Adult T-Cell Leukemia/Lymphoma Is AMPK-Independent

The authors assessed the expression of AMP-activated protein kinase (AMPK) in primary adult T-cell leukemia/lymphoma (ATL) cells and the effects of dorsomorphin, an AMPK inhibitor, on primary ATL cells and HTLV‐1‐infected T-cell lines. AMPK expression in acute and chronic ATL patients was significantly higher than in asymptomatic human T-cell leukemia virus type 1 carriers and healthy donors. [FEBS J] Abstract

Inverse Association between the Quantity of Human Peripheral Blood CXCR5⁺IFN-γ⁺CD8⁺T Cells with De Novo DSA Production in the First Year after Kidney Transplant

Scientists retrospectively and serially analyzed peripheral blood CD8⁺ and CD4⁺ T cell subsets and monitored for the development of de novo donor-specific antibody (DSA) in kidney transplant recipients during the first year post-transplant. They report results on 95 first-time human kidney transplant recipients with one year follow-up. [Transplantation] Abstract

Quantification of T Cell Binding Polyclonal Rabbit Anti-Thymocyte Globulin in Human Plasma with Liquid Chromatography Tandem-Mass Spectrometry

Researchers describe the first liquid chromatography tandem-mass spectrometry method to quantify the pharmacologically active fraction of polyclonal anti-human thymocyte globulin (ATG) in plasma. This was achieved through immunoaffinity purification of active ATG from plasma with Jurkat T cells. [AAPS J] Full Article

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CD8⁺ T Cell States in Human Cancer: Insights from Single-Cell Analysis

Investigators cover current knowledge of the T cell states that are present in human tumors and the role that different T cell populations have been hypothesized to play within the tumor microenvironment, with a particular focus on CD8⁺ T cells. [Nat Rev Cancer] Abstract

Immune Cell Regulation of Glia During CNS Injury and Disease

Recent evidence suggests that microglia, which are also the brain’s major resident immune cells, provide disease-modifying regulation of the other major glial populations, namely astrocytes and oligodendrocytes. In addition, peripheral immune cells entering the CNS after injury and in disease may directly affect microglial, astrocyte and oligodendrocyte function, suggesting an integrated network of immune cell–glial cell communication. [Nat Rev Neurosci] Abstract

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Can-Fite Completes 50% Patient Enrollment in Phase III Rheumatoid Arthritis Study and Implements Interim Analysis

Can-Fite BioPharma Ltd. announced it has completed enrollment of approximately 50% of the 525 patients planned for its Phase III ACRobat™ trial to evaluate its drug candidate Piclidenoson as a first-line treatment for rheumatoid arthritis. [Can-Fite BioPharma Ltd.] Press Release

SELLAS Announces Enrollment of First Patient in Phase I Trial of Galinpepimut-S (GPS) in Combination with Nivolumab (Opdivo^®) in Patients with Malignant Pleural Mesothelioma (MPM)

SELLAS Life Sciences Group, Inc. announced the enrollment of the first patient in an investigator-sponsored clinical trial of its Wilms tumor-1-targeting peptide immunotherapeutic agent, GPS, in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab, in patients with MPM. [SELLAS Life Sciences Group, Inc.] Press Release

Trump’s 2021 Budget Drowns Science Agencies in Red Ink, Again

It’s another sea of red ink for federal research funding programs in President Donald Trump’s latest budget proposal. The 2021 budget request to Congress released February 10^th calls for deep, often double-digit cuts to R&D spending at major science agencies. [ScienceInsider] Editorial

Major Cancer Institute Sued by Its Own Researchers over ‘Tapering’ Funding

Alleging that a leading cancer funder is slashing their support in an “unethical and reckless” way, six prominent cancer researchers at the University of California, San Diego, have filed a lawsuit to compel it to continue its current level of support. [ScienceInsider] Editorial

NEW Evolutionary Dynamics in Carcinogenesis and Response to Therapy
March 12-15, 2020
Denver, Colorado, United States

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NEW Postdoctoral Fellow – Plasma Cell Development (Western Michigan University)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Bioengineering (STEMCELL Technologies Inc.)

Postdoctoral Fellow – T and B Cells in Celiac Disease (University of Oslo)

Professorship – Antimicrobial Resistance (University Hospital of Cologne)

Research Scientist – Immuno-Oncology (Ervaxx)

Chief – Division of Immunology (Boston Children’s Hospital)

Research Assistant Professor – Immunology (The University of Chicago)

Postdoctoral Fellowship – Breast Cancer Immunology and Immunotherapy (The University of Texas Southwestern Medical Center)

Postdoctoral Fellow – Immune Defense and HIV (Massachusetts General Hospital)

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