Human Immunology News Volume 7.46 | Nov 26 2019

TOP STORY

Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8⁺ T Cells

Scientists engineered tumor-specific CD8⁺ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. [Cancer Cell] Abstract | Graphical Abstract

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Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4⁺ T Cell Pathogenicity and Suppresses Autoimmunity

Researchers report PKM2 upregulation, phosphorylation, and nuclear accumulation in murine and human CD4⁺ T cells following activation in vitro. [Cell Metab] Full Article | Graphical Abstract

Impaired ATM Activation in B Cells Is Associated with Bone Resorption in Rheumatoid Arthritis

Scientists report that a group of patients with rheumatoid arthritis (RA)A and elevated frequencies of CD21^−/lo B cells showed decreased ataxia telangiectasia-mutated (ATM) expression and activation in B cells compared with other patients with RA and healthy donor controls. [Sci Transl Med] Abstract

In Vivo Clonal Expansion and Phenotypes of Hypocretin-Specific CD4⁺ T Cells in Narcolepsy Patients and Controls

Investigators present evidence of in vivo expansion of DQ6-HCRT tetramer⁺/TRAJ24⁺/CD4⁺ T cells in DQ6⁺ individuals with and without narcolepsy. They identified related TRAJ24⁺ TCRαβ clonotypes encoded by identical α/β gene regions from two patients and two controls. [Nat Commun] Full Article

Leishmania RNA Virus Exacerbates Leishmaniasis by Subverting Innate Immunity via TLR3-Mediated NLRP3 Inflammasome Inhibition

The authors combined human and mouse data to demonstrate that Leishmania RNA virus triggerred TLR3 and TRIF to induce type I IFN production, which induces autophagy. [Nat Commun] Full Article

Missing Self Triggers NK Cell-Mediated Chronic Vascular Rejection of Solid Organ Transplants

Human in vitro models and transplantation of β2-microglobulin-deficient hearts into wild-type mice demonstrated that the inability of graft endothelial cells to provide HLA I-mediated inhibitory signals to recipient circulating NK cells triggered their activation, which in turn promoted endothelial damage. [Nat Commun] Full Article

Cancer-Derived Sialylated IgG Promotes Tumor Immune Escape by Binding to Siglecs on Effector T Cells

Using a monoclonal antibody against cancer-derived IgG (Cancer-IgG), the authors found that cancer cells could secrete IgG into the tumor microenvironment. Furthermore, cancer-IgG, which carries an abnormal sialic acid modification in the CH1 domain, directly inhibited effector T-cell proliferation and significantly promoted tumor growth by reducing CD4⁺ and CD8⁺ T-cell infiltration into tumor tissues. [Cell Mol Immunol] Abstract

The Differential Statin Effect on Cytokine Production of Monocytes or Macrophages Is Mediated by Differential Geranylgeranylation-Dependent Rac1 Activation

Investigators compared statin-dependent cytokine production of lipopolysaccharide-stimulated freshly isolated human monocytes and macrophages derived from monocytes by overnight differentiation. [Cell Death Dis] Full Article

Phosphorylation of PD-1-y248 Is a Marker of PD-1-Mediated Inhibitory Function in Human T Cells

Scientists generated an antibody specific for phosphorylated PD-1-Y248 and examined PD-1pY248⁺ (pPD-1) expression in human T cells. pPD-1 was upregulated by TCR/CD3⁺CD28 stimulation and simultaneous PD-1 ligation. pPD-1⁺CD8⁺ T cells were identified in human peripheral blood and had impaired effector function. [Sci Rep] Full Article

Single Variable Domains from the T Cell Receptor β Chain Function as Mono- and Bifunctional CARs and TCRs

Researchers describe a single-variable-domain T cell receptor (TCR) that utilized only the variable domain of the β chain (Vβ). This Vβ module not only worked in TCR and chimeric antigen receptor (CAR) formats, but also could be used to create single-chain bispecific CARs and TCRs. [Sci Rep] Full Article

Global Alteration of T-Lymphocyte Metabolism by PD-l1 Checkpoint Involves a Block of De Novo Nucleoside Phosphate Synthesis

Scientists developed and used an optimized metabolite extraction protocol for non-adherent primary human T-cells, to broadly profile in vitro metabolic changes effected by PD-1 signaling by mass spectrometry-based metabolomics and isotopomer analysis. [Cell Discov] Full Article

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Interrogating Host Immunity to Predict Treatment Response in Inflammatory Bowel Disease

The authors focus on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy. [Nat Rev Gastroenterol Hepatol] Abstract

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Dragonfly Therapeutics Announces Collaboration with AbbVie for Autoimmune Diseases and Oncology

Dragonfly Therapeutics and AbbVie announced a multi-target research collaboration designed to advance a number of Dragonfly’s novel NK cell engager-based immunotherapies for autoimmune and oncology indications. [Dragonfly Therapeutics (PR Newswire Association LLC.)] Press Release

Sangamo Announces UK Authorization of a Phase I/II Clinical Trial Evaluating the CAR-Treg Cell Therapy TX200 for Kidney Transplantation

Sangamo Therapeutics, Inc. announced that the United Kingdom’s (UK) Medicines Healthcare Products Regulatory Agency has granted authorization of the first-in-human clinical trial to evaluate a chimeric antigen receptor regulatory T cell (CAR-Treg) therapy. [Sangamo Therapeutics, Inc.] Press Release

Five Ways China Must Cultivate Research Integrity

A swift increase in scientific productivity has outstripped the country’s ability to promote rigour and curb academic misconduct; it is time to seize solutions. [Nature News] Editorial

Elsevier Signs First Open-Access Deal in the United States

Publishing giant Elsevier has signed its first open-access deal with a US institution, Carnegie Mellon University (CMU) in Pittsburgh, Pennsylvania, Inside Higher Ed reports. The arrangement, which CMU announced on 21 November, will allow CMU scholars to publish articles in any Elsevier journal on an immediately free-to-read basis. [ScienceInsider] Editorial

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NEW Postdoctoral Fellow – Autoimmune Pathogenesis (Oklahoma Medical Research Foundation)

Research Associate – Immunology (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Post-Doctoral Fellow – Cancer Immunology/Bioengineering (West Virginia University)

Postdoctoral Fellow – Infection, Inflammation and Immunology (The Boston University Pulmonary Center)

Group Leader Position – Immunology (Research Institute of Molecular Pathology)

Postdoctoral Position – B Cells (Institut Necker Enfants Malades)

Director of Operations – Immunopathogenesis (The Immunotherapy Assessment Core)

Postdoctoral Positions – Immunotherapies (Indiana University School of Medicine)

PhD Studentship – Melanoma (Cancer Research UK Manchester Institute)

Postdoctoral Position – Blood Cancer Immunology (University Children’s Hospital Basel)

Senior Scientific Researcher – Immunology Discovery (Genentech, Inc.)

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