Human Immunology News Volume 5.48 | Dec 5 2017

TOP STORY

Cell Atlas of Head and Neck Cancers Reveals Metastatic Mechanisms

By mapping gene expression at the single cell level, researchers found that a unique transition may assist the spread of head and neck tumors. [Press release from the Broad Institute discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

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Diversification of Human Plasmacytoid Predendritic Cells in Response to a Single Stimulus

The authors report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1–P3). P1-pDCs displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs adopted a dendritic morphology and adaptive immune functions. P2-pDCs displayed both innate and adaptive functions. [Nat Immunol] Abstract

Targeting Both Tumor-Associated CXCR2⁺ Neutrophils and CCR2⁺ Macrophages Disrupts Myeloid Recruitment and Improves Chemotherapeutic Responses in Pancreatic Ductal Adenocarcinoma

Investigators showed CCR2 and CXCR2 combined blockade reduces total tumor-infiltrating myeloids, promoting a more robust antitumor immune response in pancreatic adenocarcinoma compared with either strategy alone. [Gut] Full Article

T Cell Receptor β-Chains Display Abnormal Shortening and Repertoire Sharing in Type 1 Diabetes

Scientists showed, by analyzing >2 × 10⁸ TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4⁺ T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s, in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. [Nat Commun] Full Article

Metabolic Reprogramming of Human CD8⁺ Memory T Cells through Loss of SIRT1

Researchers found that human CD8⁺CD28^– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD⁺-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8⁺CD28^– T cells. [J Exp Med] Abstract

Hypoxic Lung Cancer-Derived Extracellular Vesicle miR-103a Increases the Oncogenic Effects of Tumor Associated Macrophages by Targeting PTEN

Investigators found that extracellular vesicles (EVs) derived from hypoxic lung cancers increased M2 type polarization by miR-103a transfer. Decreased PTEN levels caused by hypoxic cancer cell-derived EV miR-103a increased activation of AKT and STAT3, and expression of several immunosuppressive and pro-angiogeneic factors. [Mol Ther] Abstract | Full Article | Graphical Abstract

Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells

Patient samples from a Phase I trial of NCI IL-15 in whom either did or did not show NK cell expansion were compared to healthy donor controls. Both groups had elevated expression of inhibitory receptors and decreased cytokine production compared to controls, suggestive of T cell exhaustion among all patients prior to haplo-NK cell infusion. [Biol Blood Marrow Transplant] Abstract

A Novel Human Systemic Lupus Erythematosus Model in Humanized Mice

Researchers established and characterized a systemic lupus erythematosus (SLE) model mediated by human immune system. Injection of pristane into immunodeficient mice reconstituted with human immune system recapitulated key SLE features, including: production of human anti-nuclear autoantibodies, lupus nephritis, and pulmonary serositis. [Sci Rep] Full Article

The Choice of Cryopreservation Method Affects Immune Compatibility of Human Cardiovascular Matrices

Ice-free cryopreservation demonstrated matrix structure preservation combined with attenuated immune responses. Investigators explored the mechanisms of this diminished immunogenicity in vitro. [Sci Rep] Full Article

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Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer

Tumor necrosis factor (TNF) is a proinflammatory cytokine that coordinates tissue homeostasis by regulating cytokine production, cell survival, and cell death. However, how life and death decisions are made in response to TNF is poorly understood. [Trends Mol Med] Abstract

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Vedanta Biosciences Expands Network of Clinical Collaborations Supporting Development of Microbiome Therapeutics for Cancer Immunotherapy

Vedanta Biosciences announced new translational medicine collaborations in cancer immunotherapy with Leiden University Medical Center and the University of South Alabama Mitchell Cancer Institute. [Vedanta Biosciences, Inc.] Press Release

RXi Pharmaceuticals and the Center for Cancer Immune Therapy at Herlev Hospital Announce Research Collaboration

RXi Pharmaceuticals Corporation and the Center for Cancer Immune Therapy at Herlev Hospital announced that they have entered into a collaborative research agreement to evaluate the potential of RXi’s novel self-delivering RNAi technology platform in tumor infiltrating lymphocytes for the use in treatment for a number of cancer types, including melanoma and ovarian cancer. [RXi Pharmaceuticals Corporation] Press Release

Rise in Malaria Cases Sparks Fears of a Resurgence

Progress in the fight against a curable disease that kills hundreds of thousands of children has stalled, according to the World Health Organization. [Nature News] Editorial

Biohackers Disregard FDA Warning on DIY Gene Therapy

Despite a warning from the federal government about do-it-yourself (DIY) gene therapy, two companies say they’ll continue offering DNA-altering materials to the public. The companies, The Odin and Ascendance Biomedical, both recently posted videos online of people self-administering DNA molecules their labs had produced. [MIT Technology Review] Editorial

Trump Science Job Nominees Missing Advanced Science Degrees

When it comes to filling jobs dealing with complex science, environment, and health issues, the Trump administration is nominating people with fewer science academic credentials than their Obama predecessors. And it’s moving slower as well. [STAT News] Editorial

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NEW Postdoctoral Research Associate – Human Immunology (Benaroya Research Institute at Virginia Mason)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Positions – Immunotherapy (University of Houston)

PhD Candidate – Innate Immunity in Lung Adenocarcinoma (Helmholtz Zentrum München)

Postdoctoral Positions – Cytokines in Immunity, Stem Cells and Tissue Repair (Weill Cornell Medicine)

Postdoctoral Position – Immunology (Ghent University)

Postdoctoral Scientist – Molecular Genetics of Human T Cell Development (Ghent University)

Postdoctoral Fellow – Mucosal Immunology (University of Lorraine)

Postdoctoral Fellow – Mucosal Infections (University of Utah)

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