Human Immunology News Volume 5.23 | Jun 13 2017

TOP STORY

Pyruvate Controls the Checkpoint Inhibitor PD-L1 and Suppresses T Cell Immunity

Researchers found that macrophages from patients with coronary artery disease (CAD) actively suppress T cell activation and expansion, leading to defective varicella zoster virus-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1, thereby providing negative signals to programmed death-1⁺ T cells. [J Clin Invest] Full Article

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Ash1l and Lnc-Smad3 Coordinate Smad3 Locus Accessibility to Modulate iTreg Polarization and T Cell Autoimmunity

Investigators showed that the H3K4 methyltransferase Ash1l facilitated TGF-β-induced regulatory T (Treg) cell polarization in vitro and protected mice from T cell-mediated colitis in vivo. Ash1l upregulated Smad3 expression by directly targeting Smad3 promoter to increase local H3K4 trimethylation. They identified an lncRNA, namely lnc-Smad3, which interacted with the histone deacetylase HDAC1 and silenced Smad3 transcription. [Nat Commun] Full Article

Different TCR-Induced T Lymphocyte Responses Are Potentiated by Stiffness with Variable Sensitivity

Scientists characterized how human primary CD4⁺ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. [eLife] Full Article

Fibroblastic Reticular Cells of the Lymphoid Tissues Modulate T Cell Activation Threshold during Homeostasis via Hyperactive Cyclooxygenase-2/Prostaglandin E₂ Axis

Fibroblastic reticular cells (FRCs) in the T cell zone of lymph nodes are pivotal for T cell survival, mobility, and peripheral tolerance. The authors demonstrated that during homeostasis, FRCs also suppress T cell activation via producing high level of prostaglandin E2 due to their thousands-fold higher cyclooxygenase-2 expression than immune cells. [Sci Rep] Full Article

Fibroblast Growth Factor 23 Weakens Chemotaxis of Human Blood Neutrophils in Microfluidic Devices

Researchers examined the effect of fibroblast growth factor 23 (FGF23) on human blood neutrophil chemotaxis using two new microfluidic devices. Their results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells. [Sci Rep] Full Article

Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells

Scientists employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs in human naive, central memory, and effector memory CD4⁺ T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. [J Immunol] Abstract

Enrichment of Human CCR6⁺ Regulatory T Cells with Superior Suppressive Activity in Oral Cancer

Researchers hypothesized that oral squamous cell carcinoma may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. They found that most (60%) peripheral blood Treg cells express CCR6, and CCR6⁺ Treg cells exhibit an activated effector/memory phenotype. [J Immunol] Abstract

In Vivo Murine-Matured Human CD3⁺ Cells as a Preclinical Model for T Cell-Based Immunotherapies

Adult apheresis CD34⁺ cells engraft in neonatal non-obese diabetic-severe combined immunodeficiency-common γ chain^–/– mice and lead to the development of CD3⁺ T cells in peripheral circulation. Investigators demonstrated that these in vivo murine-matured autologous CD3⁺ T cells from humans can be collected from the mice, engineered with lentiviral vectors, reinfused into the mice, and detected in multiple lymphoid compartments at stable levels over 50 days after injection. [Mol Ther Methods Clin Dev] Full Article

Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy

Clinical improvement in stem cell gene therapy (SCGT) for primary immunodeficiencies depends on the engraftment levels of genetically corrected cells, and tracing the transgene in each hematopoietic lineage is therefore extremely important in evaluating the efficacy of SCGT. The authors established a single cell-based droplet digital PCR method consisting of the encapsulation of a single cell into each droplet, followed by emulsion PCR with primers and probes specific for the transgene. [Mol Ther Methods Clin Dev] Full Article | Graphical Abstract

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Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape

Scientists discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation dendritic cells (DCs) vaccines. They also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy. [Trends Immunol] Abstract

The Functions of Tumor Suppressor PTEN in Innate and Adaptive Immunity

The authors focus on the newly discovered functions of phosphatase and tensin homolog (PTEN) in the regulation of innate and adaptive immunity, including antiviral responses. [Mol Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

AbbVie and Principia Announce Collaboration on Oral Immunoproteasome Inhibitors

AbbVie and Principia Biopharma Inc. announced that they have entered a collaboration for the development of oral immunoproteasome inhibitors. The collaboration is aimed at developing first-in-class oral therapies that bring the power of proteasome inhibition safely into the field of immunology. [AbbVie] Press Release

OSE Immunotherapeutics Announces Strategic Multi-Year Research Collaboration with Memorial Sloan Kettering Cancer Center in New York Focused on Company’s Cytotoxic Monoclonal Antibody OSE-703 Targeting IL-7R to Treat Cancer

OSE Immunotherapeutics SA announced that the company has entered into a multi-year research collaboration on OSE-703, a cytotoxic monoclonal antibody against the alpha chain of interleukin-7 receptor (IL-7R), with Memorial Sloan Kettering Cancer Center in New York. [OSE Immunotherapeutics SA] Press Release

Intellia Therapeutics and San Raffaele University and Research Hospital to Combine CRISPR/Cas9 Genome Editing with Enhanced Cell Therapies to Fight Cancer

Intellia Therapeutics and San Raffaele University and Research Hospital have entered into a three-year research collaboration, option and license agreement to engineer optimized T cell cancer therapies. [Intellia Therapeutics, Inc.] Press Release

Dragonfly Therapeutics Announces Strategic Collaboration with Celgene to Discover and Develop Novel Natural Killer (NK) Cell-Based Immunotherapies Using Dragonfly’s TriNKET^™ Technology Platform

Dragonfly Therapeutics, Inc. announced a global strategic collaboration with Celgene Corporation and its affiliates to discover, develop and commercialize innovative immuno-oncology treatment options for patients with hematological malignancies based on Dragonfly’s NK cell based TriNKET^™ technology platform. [Dragonfly Therapeutics, Inc. (PR Newswire Association LLC.)] Press Release

Can Fake Names Tease Out NIH Reviewer Bias?

When the label “white male” is attached to a research grant application, do peer reviewers give it a better score? That’s the question psychologist Patricia Devine of the University of Wisconsin in Madison has spent the past four years, and more than $1 million from the National Institutes of Health (NIH) in Bethesda, Maryland, trying to answer with an unusual experiment. [ScienceInsider] Editorial

Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France

The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial

Trump Names Sharpless to Lead U.S. Cancer Institute

President Donald Trump announced his intention to appoint Norman “Ned” Sharpless to be the next director of the National Cancer Institute in Bethesda, Maryland. Sharpless, who is 50 years old, is a physician and currently director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. He also holds an academic appointment at the university’s school of medicine. [ScienceInsider] Editorial

NEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics
October 26-30, 2017
Philadelphia, United States

NEW American College of Allergy, Asthma, & Immunology (ACAAI)
October 26-30, 2017
Boston, Massachusetts, United States

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NEW Postdoctoral Research Fellow – Immunology (Fred Hutchinson Cancer Research Center)

Scientific Sales Representative – Cell Separation (STEMCELL Technologies Inc.)

Research Technician in Cancer Immunotherapy (University College London)

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Innate and Adaptive Immunity (Stanford University)

Postdoctoral Position – Cancer Immunology and Immunotherapy (Weill Cornell Medicine)

Scientist – Analytical Development (KBI Biopharma)

Postdoctoral Research Associate – Molecular Microbiology and Immunology (University of Southern California)

Senior Scientific Researcher – Personalized Cancer Vaccines (Genentech)

Faculty Position – Cancer Immunology (Mayo Clinic)

Postdoctoral Fellow – Innate Immunity and Neurodegeneration (Mount Sinai Health System)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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