Human Immunology News Volume 8.07 | Feb 25 2020

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A Cell Atlas of Human Thymic Development Defines T Cell Repertoire Formation

To provide a comprehensive atlas of thymic cells across human life, investigators performed single-cell RNA sequencing using dissociated cells from human thymus during development, childhood, and adult life. They sampled 15 embryonic and fetal thymi spanning thymic developmental stages between 7 and 17 post-conception weeks, as well as nine postnatal thymi from pediatric and adult individuals. [Science] Abstract | Graphical Abstract

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Human FCHO1 Deficiency Reveals Role for Clathrin-Mediated Endocytosis in Development and Function of T Cells

Scientists identified ten unrelated patients with variable T and B cell lymphopenia, who were homozygous for six distinct mutations in FCH domain only 1 (FCHO1) protein. They demonstrated that these mutations either led to mislocalisation of the protein or prevented its interaction with binding partners. Live-cell imaging of cells expressing mutant variants of FCHO1 provided evidence of impaired formation of clathrin coated pits. [Nat Commun] Full Article

Engineering Light-Controllable CAR T Cells for Cancer Immunotherapy

The authors developed a light-inducible nuclear translocation and dimerization system for gene regulation to control CAR T activation. They demonstrated light-controllable gene expression and functional modulation in human embryonic kidney 293T and Jurkat T cell lines. [Sci Adv] Full Article

Hyperactive PI3Kδ Predisposes Naive T Cells to Activation via Aerobic Glycolysis Programs

With a cohort of children with PIK3CD gain of function mutations from multiple regions of China and a corresponding CRISPR/Cas9 gene-edited mouse model, researchers reported that hyperactive PI3Kδ disrupted T_Naive cell homeostasis in the periphery by intrinsically promoting the growth, proliferation, and activation of T_Naive cells. [Cell Mol Immunol] Abstract

The Action of Echis carinatus and Naja naja Venoms on Human Neutrophils; An Emphasis on NETosis

Formation of neutrophil extracellular traps (NETs), cell viability, ROS, and Ca²⁺ levels were estimated. An in vivo toxicity study and possible cellular signaling were addressed using immunoblots and pharmacological inhibitors. [Biochim Biophys Acta] Abstract

Some Gammaproteobacteria Are Enriched within CD14⁺ Macrophages from Intestinal Lamina Propria of Crohn’s Disease Patients Versus Mucus

The 16S rRNA gene amplicon sequencing method was used to identify bacteria that were specifically present in intestinal CD14⁺CD11c⁺ macrophages of Crohn’s disease patients. Bacteria present in intestinal CD14⁺CD11c⁺ macrophages and mucus of Crohn’s disease patients were separated into different clusters in principal coordinates analysis. [Sci Rep] Full Article

Type 1 Diabetes Progression Is Associated with Loss of CD3⁺CD56⁺ Regulatory T Cells That Control CD8⁺ T-Cell Effector Functions

Researchers showed that peripheral frequency of a regulatory T cell population, characterized by the coexpression of CD3 and CD56 molecules (T_R3-56), was reduced in individuals with new-onset type 1 diabetes (T1D). In three independent T1D cohorts, they found that low frequency of circulating T_R3-56 cells was associated with reduced beta-cell function and with the presence of diabetic ketoacidosis. [Nat Metab] Abstract

Patient iPSC-Derived Macrophages to Study Inborn Errors of the IFN-γ Responsive Pathway

The authors report a disease modeling platform for studying interferon (IFN)-γ related pathologies using macrophages derived from patient specific induced pluripotent stem cells (iPSCs). They used iPSCs from patients with autosomal recessive complete- and partial IFN-γR2 deficiency, partial IFN-γR1 deficiency and complete STAT1 deficiency. [Cells] Full Article | Graphical Abstract

Combination of Chemotherapy and PD-1 Blockade Induces T Cell Responses to Tumor Non-Mutated Neoantigens

Investigators developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer cells that had been induced to apoptosis by cisplatin treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens. [Commun Biol] Full Article

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Regulatory T Cells and T Helper 17 Cells in Viral Infection

Studies have shown that T regulatory cells (Tregs) and T helper (Th)17 cells have rather complex interplays in viral infection: Th17 cells may contribute to immune activation and disease progression while Tregs may inhibit this process and play a key role in the maintenance of immune homeostasis, possibly at the cost of compromised viral control. [Scand J Immunol] Abstract

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Pediatric Researchers in Montreal Unite to Tackle Infection and Immunity on Two Different Fronts

Researchers at the Montreal Children’s Hospital of the McGill University Health Center and the CHU Sainte-Justine are coming together within the scope of two new projects, funded under the auspices of the McGill Interdisciplinary Initiative in Infection and Immunity: improving the diagnosis and treatment of bacterial pneumonia and better understanding rare immune disorders. [McGill University] Press Release

Immatics and GSK Partner to Develop Novel Adoptive Cell Therapies

Immatics Biotechnologies GmbH announced it has entered into a strategic collaboration agreement with GSK to develop novel adoptive cell therapies targeting multiple cancer indications. [Immatics Biotechnologies GmbH] Press Release

IMV Inc. Announces Breakthrough Data from DeCidE1, Its Ongoing Phase II Study of DPX-Survivac in Patients with Advanced Recurrent Ovarian Cancer

IMV Inc. reported updated results from DeCidE1, an ongoing Phase II study of its lead candidate, DPX-Survivac, in patients with advanced recurrent ovarian cancer. The results show that DPX-Survivac immunotherapy is active and well-tolerated in patients with advanced ovarian cancer. [IMV Inc.] Press Release

Five Prime Therapeutics Licenses Antibodies to Seattle Genetics for Use in Novel Antibody Drug Conjugate (ADC) Programs

Five Prime Therapeutics, Inc. announced a global license agreement with Seattle Genetics, Inc. to develop and commercialize novel ADC therapies using monoclonal antibodies developed by Five Prime. [Five Prime Therapeutics, Inc.] Press Release

MeTooSTEM Organization Reeling after More Resignations

The prominent nonprofit group MeTooSTEM appears to be imploding amid resignations and accusations of bullying by founder BethAnn McLaughlin. Critics, many of whom are antiharassment advocates, say she has sidelined people of color and bullied volunteers, activists, and fellow leaders both at the nonprofit and outside of it. [ScinceInsider] Editorial

Has the UK Science Minister Been Demoted?

A government reshuffle in the United Kingdom has born another new science minister – a position that has seen a revolving door of appointees, firings and resignations in recent years. The latest appointment also comes with an apparent political demotion for the role, which expert observers say is in conflict with a government that appears to have put research and innovation at the heart of its agenda. [Nature News] Editorial

NIH Hosts Nonhuman Primate Workshop amidst Increased Scrutiny of Monkey Research

More than three years after it hosted a workshop on the science and ethics of biomedical studies on monkeys, the National Institutes of Health (NIH) convened another workshop on nonhuman primate research. And much like the previous event, the meeting is drawing sharply divergent reactions from biomedical and animal advocacy groups. [ScienceInsider] Editorial

NEW T-ALL 2020, Omics, Biology and Therapy
March 20-22, 2020
Utrecht, Netherlands

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NEW Postdoctoral Researcher – Cancer Immunotherapy (German Cancer Research Center in the Helmholtz Association)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

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

Postdoctoral Fellow – Plasma Cell Development (Western Michigan University)

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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