Human Immunology News Volume 6.14 | Apr 10 2018

TOP STORY

Increased Tumor Glycolysis Characterizes Immune Resistance to Adoptive T Cell Therapy

Overexpression of glycolysis-related molecules impaired T cell killing of tumor cells, whereas inhibition of glycolysis enhanced T cell-mediated antitumor immunity in vitro and in vivo. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Alternative Splicing of FOXP3 Controls Regulatory T Cell Effector Functions and Is Associated with Human Atherosclerotic Plaque Stability

Regulatory T (Treg) cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3Δ2. FOXP3Δ2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-β to the cell membrane of activated Treg cells. [Circ Res] Abstract

How Biophysical Forces Regulate Human B Cell Lymphomas

Investigators showed that fluid flow enhances proliferation and modulates response of diffuse large B cell lymphomas (DLBCLs) to specific therapeutic agents. Fluid flow upregulates surface expression of B cell receptors (BCRs) and integrin receptors in subsets of ABC-DLBCLs with either CD79A/B mutations or WT BCRs, similar to what is observed with xenografted human tumors in mice. [Cell Rep] Full Article | Press Release | Graphical Abstract

A Nanoscale Reorganization of the IL-15 Receptor Is Triggered by NKG2D in a Ligand-Dependent Manner

Using superresolution microscopy, the authors found that natural killer group 2D (NKG2D) is constitutively arranged in nanoclusters at the surface of human primary natural killer cells. [Sci Signal] Abstract

Human CD19-Targeted Mouse T-Cells Induce B-Cell Aplasia and Toxicity in Human CD19 Transgenic Mice

To elucidate the underlying toxicity mechanisms and test potentially safer CAR T-cells, scientists developed a mouse model in which human CD19 (hCD19)-specific mouse CAR T-cells were adoptively transferred into mice whose normal B-cells express a hCD19 transgene at hemizygous levels. [Mol Ther] Abstract

Induction of a Central Memory and Stem Cell Memory Phenotype in Functionally Active CD4⁺ and CD8⁺ CAR T Cells Produced in an Automated Good Manufacturing Practice System for the Treatment of CD19⁺ Acute Lymphoblastic Leukemia

Researchers set up a protocol for anti-CD19 CAR T-cell generation aiming at high central memory T cells/stem cell-like memory T cells numbers. 100 ml peripheral blood from pediatric pre-B-precursor acute lymphoblastic leukemia patients was processed including CD4⁺/CD8⁺-separation, T-cell activation with modified anti-CD3/-CD28 reagents and transduction with a 4-1BB-based second generation CAR lentiviral vector. [Cancer Immunol Immunother] Abstract

Silent Infection of Human Dendritic Cells by African and Asian Strains of Zika Virus

With the aim to identify virus lineage-dependent factors, scientists compared cell susceptibility, virus replication, cell death and innate immune responses following infection with two African and three contemporary Asian lineage strains of Zika virus. To this end, they used green monkey Vero and Aedes albopictus C6/36 cells and human monocyte-derived dendritic cells. [Sci Rep] Full Article

Compromised Functionality of Monocyte-Derived Dendritic Cells in Multiple Myeloma Patients May Limit Their Use in Cancer Immunotherapy

The authors investigated whether in vitro generated monocyte-derived dendritic cells (DCs) from multiple myeloma (MM) patients (MM-DCs) possess impaired functionality, thus contributing to the limited success of DC vaccines. They generated MM-DCs and compared them with DCs from healthy donors. [Sci Rep] Full Article

Anti-TNF and Thiopurine Therapy in Pregnant IBD Patients Does Not Significantly Alter a Panel of B-Cell and T-Cell Subsets in 1-Year-Old Infants

Investigators immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD. They analyzed samples from infants exposed to infliximab (IFX) or adalimumab (ADA) monotherapy, certolizumab pegol (CZP) monotherapy, IFX or ADA plus thiopurine combination therapy, and CZP plus thiopurine combination therapy. [Clin Transl Gastroenterol] Full Article

B Lymphocytes Confer Immune Tolerance via Cell Surface GARP-TGF-β Complex

Although B cells do not express GARP at baseline, researchers found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell–independent antibody production. [JCI Insight] Full Article

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Understanding Lymphocyte Metabolism for Use in Cancer Immunotherapy

The authors highlight some of the recent knowledge on T lymphocyte metabolism and give a perspective on the practical implications for cellular-based immunotherapy. [FEBS J] Abstract | Full Article

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Pfizer and Allogene Therapeutics Enter into Asset Contribution Agreement for Pfizer’s Allogeneic CAR T Immuno-Oncology Portfolio

Pfizer Inc. and Allogene Therapeutics, Inc. announced that the two companies have entered into an asset contribution agreement for Pfizer’s portfolio of assets related to allogeneic CAR T therapy, an investigational immune cell therapy approach to treating cancer. [Pfizer Inc.] Press Release

Bioniz Therapeutics Initiates Phase I/II Clinical Study of BNZ-1 in T-Cell Leukemia and Lymphoma

Bioniz Therapeutics, Inc. announced that it has initiated a Phase I/II open-label clinical study of its lead product candidate BNZ-1 in patients with large granular lymphocyte leukemia or refractory cutaneous t-cell lymphoma. [Bioniz Therapeutics, Inc.] Press Release

Web of Science Owner Buys Tool that Offers One-Click Access to Journal Articles

The owner of the large scholarly search engine Web of Science — Clarivate Analytics — has bought a start-up company whose tool gives researchers one-click, legal access to journal articles even when off campus. [Nature News] Editorial

India Creates Unique Tiered System to Punish Plagiarism

The Indian government has adopted its first regulations on academic plagiarism—rules that some researchers say are too lenient and others fear go too far and will be difficult to implement. [ScienceInsider] Editorial

Got Data? Survey of 2017 March for Science Doesn’t Make the Grade

A group of researchers has released the first results of a large survey of those who participated in and supported last year’s March for Science. Some social scientists say the analysis is fundamentally flawed and reflects poorly on an organization that champions scientific rigor. [ScienceInsider] Editorial

Science’s Vast Gender Pay Gap Revealed in UK Wage Data

Many UK science employers pay women much less than men, and some institutions are far less equal than others, according to an analysis conducted by Nature of statistics released last week. [Nature News] Editorial

NEW Keystone Symposia: B Cells: Mechanisms in Immunity and Autoimmunity
June 17-21, 2018
Dresden, Germany

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

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

Assistant/Associate Professor – Immunology (Saint Louis University)

Postdoctoral Fellow – Allergic Disease Inflammation Research (La Jolla Institute for Allergy & Immunology)

Postdoctoral Position – Immune Oncology (H. Lee Moffitt Cancer & Research Institute)

Scientist – Immune Tolerance (Moderna Therapeutics)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Research Associate – Immunity and Inflammation (University of Illinois)

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