Human Immunology News Volume 8.14 | Apr 14 2020

TOP STORY

Transcriptional Profiling and Therapeutic Targeting of Oxidative Stress in Neuroinflammation

Transcriptional profiling of oxidative stress–producing CNS innate immune cells identified a core oxidative stress gene signature coupled to coagulation and glutathione-pathway genes shared between a microglia cluster and infiltrating macrophages. [Nat Immunol] Abstract

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CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted neutrophil extracellular trap (NET)osis. NETs wrapped and coated tumor cells and shielded them from cytotoxicity, as mediated by CD8⁺ T cells and NK cells, by obstructing contact between immune cells and the surrounding target cells. [Immunity] Abstract | Graphical Abstract

Single-Cell Transcriptomics Identifies an Effectorness Gradient Shaping the Response of CD4⁺ T Cells to Cytokines

Investigators used quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naïve and memory CD4⁺ T cells to show that responses to cytokines differed substantially between these cell types. Memory T cells were unable to differentiate into the Th2 phenotype, and acquired a Th17-like phenotype in response to iTreg polarization. [Nat Commun] Full Article | Press Release

Potent BRD4 Inhibitor Suppresses Cancer Cell-Macrophage Interaction

The authors report the discovery and characterization of NHWD-870, a bromodomain and extraterminal domain (BET) inhibitor that was more potent than three major clinical stage BET inhibitors BMS-986158, OTX-015, and GSK-525762. NHWD-870 caused tumor shrinkage or significantly suppresses tumor growth in nine xenograft or syngeneic models. [Nat Commun] Full Article

Neoadjuvant PROSTVAC Prior to Radical Prostatectomy Enhances T-Cell Infiltration into the Tumor Immune Microenvironment in Men with Prostate Cancer

An open-label, Phase II study of neoadjuvant PROSTVAC vaccine enrolled 27 patients with localized prostate cancer awaiting radical prostatectomy. Researchers evaluated increases in CD4 and CD8 T-cell infiltrates using a six-color multiplex immunofluorescence Opal method. [J Immunother Cancer] Full Article

A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity

Scientists describe a xenograft model of off-tumor CAR-T cell-associated toxicity. Human CAR-T cells targeted against HER2 using a small protein binding domain induced acute, dose-dependent toxicities in mice. [Mol Ther] Abstract | Full Article | Graphical Abstract

Distinct Notch1 and BCL11B Requirements Mediate Human γδ/αβ T Cell Development

The authors showed that Notch1 activation was more stringently required for human γδ development compared to αβ-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. [EMBO Rep] Abstract | Graphical Abstract

Immunomodulatory Role of Interleukin-33 in Large Vessel Vasculitis

Investigators examined the role of IL-33 in the immunomodulation of T cell activation in large vessels vasculitis. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis and 50 healthy donors, using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. [Sci Rep] Full Article

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Researchers investigated the influence of myeloid progenitors on CD34⁺ cell differentiation into CD56⁺ innate lymphocytes. Sorted CD34⁺ cells cultured in the presence of stem cell factor and FMS-like tyrosine kinase 3 ligand gave rise to numerous cell types, including progenitors that expressed the prolactin receptor. [Sci Rep] Full Article

Diversity of Peripheral Blood Human NK Cells Identified by Single-Cell RNA Sequencing

The authors report single-cell RNA sequencing of NK cells, comparing gene expression in unstimulated and IL-2-activated cells from healthy cytomegalovirus-negative donors. [Blood Adv] Full Article | Graphical Abstract

Co-Expression of FOXP3 and a Helios Isoform Enhances the Effectiveness of Human Engineered Regulatory T Cells

Investigators generated engineered T regulatory cells (eTregs) by retrovirally transducing total human T cells with FOXP3 alone or with each of the 2 predominant isoforms of Helios. Expression of both FOXP3 and the full-length isoform of Helios was required for eTreg-mediated disease delay in a xenogeneic graft-versus-host disease model. [Blood Adv] Full Article

Molecular Bases for HOIPINs-Mediated Inhibition of LUBAC and Innate Immune Responses

Scientists identified small-molecule chemical inhibitors of LUBAC, HOIPIN-1 and HOIPIN-8. They showed that HOIPINs down-regulated not only the proinflammatory cytokine-induced canonical NF-κB pathway, but also various pathogen-associated molecular pattern-induced antiviral pathways. [Commun Biol] Full Article

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Harnessing Therapeutic IgE Antibodies to Re-Educate Macrophages against Cancer

The authors review pre-clinical studies, which indicate control of cancer growth by tumor antigen-specific IgE that recruit and re-educate tumor-associated macrophages towards activated profiles. The clinical development harnessing the anti-tumor potential of recombinant IgE antibodies in cancer patients is also discussed. [Trends Mol Med] Abstract

The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation

Taking into consideration the role identified for miRNAs in relation to inflammatory cytokines, scientists review their participation in neoplastic progression. The involvement of miRNAs with some important transcription factors and proteins closely associated with inflammation during cancer has also been discussed. [Mol Ther] Abstract

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

Fate Therapeutics Announces Worldwide Collaboration with Janssen for Novel iPSC-Derived Cell-Based Cancer Immunotherapies

Fate Therapeutics, Inc. announced a global collaboration and option agreement with Janssen Biotech, Inc. (Janssen). Under the multi-year collaboration agreement, Janssen will contribute proprietary antigen binding domains for up to four tumor-associated antigen targets. The company will apply its induced pluripotent stem cell (iPSC) product platform to research and preclinically develop new iPSC-derived CAR NK and CAR T-cell product candidates. [Fate Therapeutics, Inc.] Press Release

How Scientists Can Volunteer to Help Fight COVID-19

Around the world, bench scientists other than those actively studying the pandemic have largely been forced to scale back or even shut down their experiments out of COVID-19 precautions. But that doesn’t mean their skills and expertise can’t contribute to the worldwide effort to address the disease. [The Scientist] Editorial

After Claims of Sex Bias, Scientific Leader at NIH’s Child Health Institute Withdraws from New Job

Constantine Stratakis, the geneticist who directed intramural science at the National Institute of Child Health and Human Development for the past decade, withdrew from a position he was slated to take in June as executive director and chief scientific officer of the Research Institute of the McGill University Health Centre in Montreal, Canada. [ScienceInsider] Editorial

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NEW Scientist – Post-Injury Inflammation (Athersys, Inc.)

Senior Scientist – Oncology Biomarker Development (Genentech, Inc.)

Associate Professor – Cancer Biology (University of Cincinnati)

Scientist – Cancer Immunology and Immunotherapy (Genentech, Inc.)

Co-Director – Anti-Cancer Immune Response (Rutgers Cancer Institute of New Jersey)

Research Fellow – Mucosal Immunology (University of Michigan)

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

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

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)

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

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