Human Immunology News Volume 8.09 | Mar 10 2020

TOP STORY

Minimal PD-1 Expression in Mouse and Human NK Cells under Diverse Conditions

Researchers assessed PD-1 expression on NK cells using multiple sources and readouts. Primary human tumor samples, ex vivo culturing, mouse tumors and viral models were all assessed using flow cytometry, qRT-PCR and RNA sequencing. [J Clin Invest] Abstract | Full Article

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A Population of Proinflammatory T Cells Coexpresses αβ and γδ T Cell Receptors in Mice and Humans

Hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR-mediated positive selection into CD4⁺ or CD8⁺ thymocytes, and constituted up to 10% of TCRδ⁺ cells in lymphoid organs. They expressed high levels of IL-R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. [J Exp Med] Abstract

The Impact of Cell-Expansion and Inflammation on the Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells

Investigators established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was performed during cell-expansion and inflammatory priming of AT-MSCs. [J Clin Med] Abstract | Download Full Article

Peptide Cargo Tunes a Network of Correlated Motions in Human Leukocyte Antigens

The authors found that different peptide sequences affect peptide-human leukocyte antigen (pHLA) flexibility in different ways, with the peptide cargo tuning a network of correlated motions throughout the pHLA complex, including in areas remote from the peptide binding interface, in a manner that could influence T cell antigen discrimination. [FEBS J] Abstract

mRNA Transfection-Induced Activation of Primary Human Monocytes and Macrophages: Dependence on Carrier System and Nucleotide Modification

Scientists established conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. [Sci Rep] Full Article

CTLA-4 Blockade Boosts the Expansion of Tumor-Reactive CD8⁺ Tumor-Infiltrating Lymphocytes in Ovarian Cancer

Researchers used a CTLA-4-blocking antibody, added during the initial tumor-infiltrating lymphocytes (TIL) culture, and found that the blockade of CTLA-4 favored the propagation of CD8⁺ TILs from ovarian tumor fragments. Adding the CTLA-4 blocking antibody in the initial phase of the TIL culture resulted in more potent anti-tumor TILs in comparison to standard TIL cultures. [Sci Rep] Full Article

Dibutyltin Alters Immune Cell Production of the Pro-Inflammatory Cytokines Interleukin (IL) 1β and IL-6: Role of Mitogen-Activated Protein Kinases and Changes in mRNA

Monocyte-depleted peripheral blood mononuclear cells (PBMCs) were exposed to dibutyltin (DBT) at concentrations of 5, 2.5, 1, 0.5, 0.25, 0.1, and 0.05μM for one, six, and 24 hours and the production of both IL-1β and IL-6 were measured. Effects of selected DBT exposures on cytokine production were also examined in PBMCs and DBT’s effects were similar when monocytes were present. [J Appl Toxicol] Abstract

Celiac Disease Risk Stratification Based on HLA-DQ Heterodimer (HLA-DQA1 ~ DQB1) Typing in a Large Cohort of Adults with Suspected Celiac Disease

The study cohort included 24,339 adult patients with suspected Celiac disease (CeD) and immunoglobulin (Ig)A sufficiency whose samples were assessed at Mayo Clinic Laboratories for HLA-DQ genotyping, total IgA, and tissue transglutaminase-IgA. Data from a subset of the patients who had duodenal biopsies were analyzed to determine the risk gradient of CeD. [Hum Immunol] Abstract

Propionate Supplementation Promotes the Expansion of Peripheral Regulatory T-Cells in Patients with End-Stage Renal Disease

Investigators evaluated the effect of the short-chain fatty acid propionate on the chronic inflammatory state and T-cell composition in end-stage renal disease (ESRD) patients. Analyzing ESRD patients and healthy blood donors before, during, and 60 days after the propionate supplementation by multiparametric flow cytometry, they observed a gradual and significant expansion in the frequencies of CD25^highCD127⁻ T regulatory cells in both groups. [J Nephrol] Full Article

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The Emerging Roles of Eosinophils in Mucosal Homeostasis

A number of key studies over the past decade have placed this restricted view of eosinophil function into question, presenting additional evidence for eosinophils as critical regulators of various homeostatic processes including immune maintenance, organ development, and tissue regeneration. [Mucosal Immunol] Full Article

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Zydus and XOMA Announce IL-2-Based Immuno-Oncology Therapy Licensing Agreement

Zydus Cadila and XOMA Corporation announced they have entered into a licensing agreement to advance an IL-2-based immuno-oncology drug candidate that combines Zydus’ IL-2 with XOMA’s novel anti-IL-2 monoclonal antibody. [Zydus Cadila,] Press Release

First Patient Dosed in IPH5201 Phase I Clinical Trial in Advanced Solid Tumors

Innate Pharma SA announced that the first patient was dosed in a Phase I clinical trial evaluating IPH5201, an anti-CD39 blocking monoclonal antibody, in adult patients with advanced solid tumors. The purpose of the study, which is sponsored by AstraZeneca, is to evaluate IPH5201 as monotherapy and in combination with durvalumab with or without oleclumab. [Innate Pharma SA (GlobeNewswire, Inc.)] Press Release

Pandion Announces First Subject Dosed in a Phase I Clinical Trial of PT101, an IL-2 Mutein Fc Fusion Therapy for Autoimmune Disease

Pandion Therapeutics, Inc. announced the dosing of the first subject in a Phase I clinical trial of PT101, a novel and proprietary IL-2 mutein Fc fusion protein therapy. PT101 has shown potential to treat autoimmune diseases by expanding populations of regulatory T cells. [Pandion Therapeutics, Inc. (Business Wire, Inc.)] Press Release

Clinical Research Company Sued Over Stolen Trade Secrets After Employee Filmed Dogs Used in Experiments

Nearly two years ago, Charles River Laboratories paid $800 million for a company called MPI Research to bolster its business running clinical trials for drug makers and other companies. But Charles River did not know one MPI employee was an also undercover agent for the Humane Society of the United States and secretly filmed experiments conducted on various dogs, which were later publicized on the internet. [STAT News] Editorial

New Trump Rules Aim to Fuel Sharing of Patient Health Records by Smartphone

President Trump’s top health care aides said they will finalize federal rules requiring health providers and insurers to make health records available to patients in an easily accessible electronic format, a policy shift aimed at fueling broader efforts to use patient data to develop new software tools and services. [STAT News] Editorial

NEW World Vaccine Congress
April 6-9, 2020
Washington, DC, United States

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NEW Faculty Member – Neuro-Oncology (Wake Forest School of Medicine)

NEW Postoctoral Scientist – Molecular and Cellular Immunology (Technical University of Munich)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Adoptive T-Cell Therapies (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Moffitt Cancer Center and Research Institute)

Postdoctoral Researchers – B Lymphocyte Regulation (NIH National Institute on Aging)

Project Leader – Innate Immune Sensing (Helmholtz Institute for RNA-Based Infection Research)

Research Fellow – Angiogenesis in Immune Regulation and Homing (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Plasma Cell Development (Western Michigan University)

Research Scientist – Immuno-Oncology (Ervaxx)

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