Human Immunology News Volume 7.45 | Nov 19 2019

TOP STORY

Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways

The authors report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn’s disease, and ulcerative colitis. They demonstrated disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP-response signaling. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy

Immune checkpoint therapy (ICT) in the subcutaneous castration-resistant prostate cancer (CRPC) model significantly increased intra-tumoral T_h1 subsets and improved survival. However, ICT failed to elicit an anti-tumor response in the bone CRPC model despite an increase in the intra-tumoral CD4 T cells, which are polarized to T_h17 rather than T_h1 lineage. [Cell] Abstract | Press Release | Graphical Abstract

RNA-Binding Protein Isoforms ZAP-S and ZAP-L Have Distinct Antiviral and Immune Resolution Functions

Investigators found that isoforms of the RNA-binding protein ZAP functioned as both a direct antiviral restriction factor and an interferon-resolution factor. [Nat Immunol] Abstract

Activated Leukocyte Cell Adhesion Molecule Regulates B Lymphocyte Migration across Central Nervous System Barriers

Scientists demonstrated that activated leukocyte cell adhesion molecule identified subsets of proinflammatory B lymphocytes and drove their transmigration across different central nervous system barriers in mouse and human. [Sci Transl Med] Abstract

Repurposing Endogenous Immune Pathways to Tailor and Control Chimeric Antigen Receptor T Cell Functionality

Investigators inserted the chimeric antigen receptor (CAR) into the TCRα gene (TRAC_CAR), and IL-12P70 into either IL2Rα or PDCD1 genes. This process resulted in transient, antigen concentration-dependent IL-12P70 secretion, increased TRAC_CAR T cell cytotoxicity and extended survival of tumor-bearing mice. [Nat Commun] Full Article

Highly Efficient Multiplex Human T Cell Engineering without Double-Strand Breaks Using Cas9 Base Editors

Scientists applied base editor technology for multiplex gene modification in primary human T cells in support of an allogeneic CAR-T platform and demonstrated that base editor can mediate highly efficient multiplex gene disruption with minimal double-strand break induction. [Nat Commun] Full Article

Intra-Lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity

The authors showed that subset-specific natural killer cell proliferation kinetics correlate with mTOR activation, and global repertoire diversity was maintained through a high degree of intra-lineage subset plasticity during interleukin-15-driven homeostatic proliferation in vitro. [Cell Rep] Abstract | Graphical Abstract

Single-Cell TCR Sequencing of Gut Intraepithelial γδ T Cells Reveals a Vast and Diverse Repertoire in Celiac Disease

Researchers found that celiac disease, patients, both untreated and treated, had larger and more diverse γδ T-cell receptor (TCR) repertoires, more frequent usage of TRDV1 and TRDV3 and different patterns of TCRγ/TCRδ-pairing compared with controls. [Mucosal Immunol] Abstract

Tumor Necrosis Factor Induces Rapid Down-Regulation of TXNIP in Human T Cells

Scientists found that naïve T cells expressed high levels of thioredoxin interacting protein (TXNIP) and that treatment of blood samples with TNF resulted in rapid down-regulation of TXNIP in the T cells. [Sci Rep] Full Article

PD-1⁺ Melanocortin Receptor Dependent-Treg Cells Prevent Autoimmune Disease

Investigators showed that blocking the PD-1/PD-L1 pathway prevented suppression of uveoretinitis (EAU) by post-EAU regulatory T cells (Tregs). Adenosine 2-A receptor induction of PD-1⁺FoxP3⁺ Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. [Sci Rep] Full Article

Transcriptional Programming and T Cell Receptor Repertoires Distinguish Human Lung and Lymph Node Memory T Cells

Using T cell receptor analysis, scientists determined the clonal overlap between memory T cell subsets within the lung and within the lung draining lymph node, and this was greater than the clonal overlap observed between memory T cell subsets compared across tissues. [Commun Biol] Full Article

Trispecific Antibodies Enhance the Therapeutic Efficacy of Tumor-Directed T Cells through T Cell Receptor Co-Stimulation

The authors developed a trispecific antibody that interacted with CD38, CD3 and CD28 to enhance both T cell activation and tumor targeting. The engagement of both CD3 and CD28 afforded efficient T cell stimulation, whereas the anti-CD38 domain directed T cells to myeloma cells, as well as to certain lymphomas and leukemias. [Nat Cancer] Abstract

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B Cells in Autoimmune and Neurodegenerative Central Nervous System Diseases

The success of B cell-depleting therapy in patients with multiple sclerosis and central nervous system (CNS) diseases with an autoantibody component, such as neuromyelitis optica spectrum disorder and autoimmune encephalitides, has underscored the role of B cells in both cellular and humoral-mediated CNS conditions. [Nat Rev Neurosci] Abstract

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Editas Medicine and Celgene Corporation Amend Existing Collaboration to Develop and Commercialize Autologous and Allogeneic T Cell Medicines for the Treatment of Cancer and Autoimmune Diseases

Editas Medicine, Inc. announced an amended collaboration with Celgene Corporation under which the parties may research, develop, and commercialize autologous and allogeneic alpha-beta T cell medicines for the treatment of cancer and autoimmune diseases. [Editas Medicine, Inc.] Press Release

Kiadis Pharma Changes Strategy to Focus Solely on Development of Natural Killer (NK) Cell Therapeutics and Terminates Development of ATIR101

Kiadis Pharma NV announced that it has completed a strategic portfolio review and has decided to change its strategy and focus all resources and investments on the company’s NK-cell therapy platform and product candidates. [Kiadis Pharma NV] Press Release

The Science Institutions Hiring Integrity Inspectors to Vet Their Papers

Some researchers have their manuscripts screened for errors before they go to journals. [Nature News] Editorial

Foreign Interference Fears Prompt Guidelines for Australian Universities

New guidelines will help Australian universities protect themselves against foreign interference, says the country’s government. The advice follows concerns that foreign groups or governments, such as the government of China, might be seeking to instigate campus activities that are against Australia’s interests. [Nature News] Editorial

Violent Clashes at Hong Kong Universities Disrupt Research

Three universities in Hong Kong have cancelled classes on campus for the rest of the term after violent clashes between police and protestors erupted in the grounds. At least another four universities have also cancelled classes — in some cases for the rest of the year — over safety concerns. [Nature News] Editorial

NEW 12^th European Lupus Meeting
March 25-27, 2020
Bruges, Belgium

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

Research Associate – Immunology (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

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.)

Senior Associate Scientist – Molecular and Cellular Neuroimmunology (Amgen)

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