Human Immunology News Volume 5.26 | Jul 4 2017

TOP STORY

New Insights into Why the Immune System Fails to See Cancer

A team of investigators at Brigham and Women’s Hospital have uncovered a critical strategy that some cancers may be using to cloak themselves – they found evidence of this genetic program across 30 human cancers of the peripheral tissue, including melanoma skin cancer. [Press release from Brigham and Women’s Hospital discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Transcriptomic Analysis of Purified Human Cortical Microglia Reveals Age-Associated Changes

The authors present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). [Nat Neurosci] Full Article

In Silico Modeling Identifies CD45 as a Regulator of IL-2 Synergy in the NKG2D-Mediated Activation of Immature Human NK Cells

Scientists investigated the interplay between the signaling pathways stimulated by the cytokine interleukin-2 (IL-2) and the activating receptor natural killer (NK)G2D in immature (CD56^bright) and mature (CD56^dim) subsets of human primary NK cells using mass cytometry experiments and in silico modeling. [Sci Signal] Abstract

Human In Vitro-Induced Regulatory T Cells Display Dlgh1 Dependent and PKC-θ Restrained Suppressive Activity

The authors report that human induced regulatory T cells (iTregs) generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. [Sci Rep] Full Article

Extraordinarily Potent Proinflammatory Properties of Lactoferrin-Containing Immunocomplexes against Human Monocytes and Macrophages

LTF (lactoferrin) is a multifunctional protein capable of activating innate immune cells via various surface receptors, researchers hypothesized that LTF-containing immune complexes (ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. [Sci Rep] Full Article

Curtailed T-Cell Activation Curbs Effector Differentiation and Generates CD8⁺ T Cells with a Naturally-Occuring Memory Stem Cell Phenotype

Scientists showed that curtailed T-cell receptor stimulation curbs human effector CD8⁺ T-cell differentiation and allows the generation of CD45RO^–CD45RA⁺CCR7⁺CD27⁺CD95⁺ -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T memory stem cells. These cells proliferated extensively in vitro and in vivo, expressed low amounts of effector-associated genes and transcription factors and underwent considerable self-renewal in response to IL-15 while retaining effector differentiation potential. [Eur J Immunol] Abstract

Dose-Dependent Responses of I3C and DIM on T-Cell Activation in the Human T Lymphocyte Jurkat Cell Line

The authors investigated indole-3-carbinol (I3C) and dimer diindolylmethane (DIM)’s dose-dependent effects on cytokines production in human T lymphocytes Jurkat cell line. Their results showed that I3C and DIM pretreatment, at higher concentrations significantly increased PMA/ionomycin-induced interleukin-2, interleukin-8 and tumor necrosis factor-α production, measured by real time polymerase chain reaction and enzyme linked immunosorbent assay. [Int J Mol Sci] Full Article

The Effect of IL-21 and CD4⁺ CD25⁺⁺ T Cells on Cytokine Production of CD4⁺ Responder T Cells in Patients with Myasthenia Gravis

Cytokine-related mechanisms that may lead to the defect of regulatory T were investigated in patients with anti-acetylcholine receptor antibody positive myasthenia gravis. Proliferation and cytokine production of responder T cells in response to polyclonal activation were measured in a suppression assay. The effect of IL-21 on suppression was evaluated in vitro in co-culture. [Clin Exp Immunol] Abstract

T Cell Activation and Differentiation Is Modulated by a CD6 Domain 1 Antibody Itolizumab

In in vitro experiments, investigators showed that by day three of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a helper T-cell (Th)17 polarizing milieu, 15–35% of CD4⁺ T-cells overexpressed CD6 and there was an establishment of differentiated Th17 cells. Addition of Itolizumab reduced the activation and differentiation of T cells to Th17 cells and decreased production of IL-17. [PLoS One] Full Article

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Mitochondrial Control of Immunity: Beyond ATP

Researchers discuss how mitochondrial metabolism varies across different immune cell subsets, how metabolic signaling dictates cell fate and how this signaling could potentially be targeted therapeutically. [Nat Rev Immunol] Abstract

Regulation of the Immune System by Laminins

The authors summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. The role of the laminins in autoimmune diseases and transplantation is discussed. [Trends Immunol] Abstract

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Servier and Transgene Have Become Partners to Apply Viral Vectorization Technology to the Engineering of Allogenic CAR-T

Servier and Transgene announced the signature of a research agreement on the application of viral vectorization technology for the production of allogenic CAR-T cell therapies. The aim is to obtain more efficient products for patients. [Servier] Press Release

Multiple Myeloma Research Foundation (MMRF) Announces $15 Million Investment in Immunotherapy Initiative

The MMRF announced that it is investing $15 million over the next three years to launch its immunotherapy initiative. The Initiative is an effort to fund the many urgent needs and areas of potential in immunotherapy. [The Multiple Myeloma Research Foundation] Press Release

NOXXON Announces First Patients Treated in Phase I/II Clinical Trial of NOX-A12 Combined with Keytruda^® in Metastatic Pancreatic and Colorectal Cancer

NOXXON Pharma N.V. announced that the first patients were treated in its Phase I/II clinical trial in patients with metastatic colorectal and pancreatic cancer at the National Center for Tumor Diseases in Heidelberg, Germany. The goal of the trial is to evaluate safety and the effects of NOX-A12 as a monotherapy on immune cell infiltration into tumors in addition to safety and efficacy of NOX-A12 in combination with Keytruda^®. [NOXXON Pharma N.V.] Press Release

First in Human Administration of UCART123 in Cellectis’ AML Phase I Clinical Trial at Weill Cornell Medicine, New York-Presbyterian Hospital

Cellectis announced the first administration in the Phase I clinical study in acute myeloid leukemia (AML) for its investigational product UCART123, one of the company’s wholly-controlled TALEN^® gene-edited product candidates. This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate targeting CD123 to be investigated in clinical trials. [Cellectis] Press Release

eTheRNA Immunotherapies Advances In Vivo mRNA Cancer Immunotherapy into First Oncology Clinical Studies

eTheRNA immunotherapies announced the start of the first Phase Ib oncology clinical study evaluating its novel candidate TriMix-MEL in metastatic melanoma patients showing no evidence of disease after surgical removal of their tumor, but at risk for disease recurrence. [eTheRNA immunotherapies] Press Release

House Lawmakers Balk at Most Trump Science Cuts in Early Bills

No. That’s the first official answer from lawmakers in the U.S. House of Representatives to President Donald Trump’s request to make deep budget cuts at several key science funding agencies. [ScienceInsider] Editorial

Europe’s next Big Science-Funding Program Urged to Double Its Budget

Midway through the European Union’s sprawling seven-year, €75-billion research-funding program known as Horizon 2020, scientists are already angling for more money and less red tape in its successor. [Nature News] Editorial

Germany and Poland Launch Research ‘Twinning’ Effort

Germany and Poland are to jointly fund top scientists to start research groups at Polish institutes, in a scheme that could provide a new blueprint for east–west research collaboration in the European Union. [Nature News] Editorial

Vaccine Ruling from Europe’s Highest Court Isn’t as Crazy as Scientists Think

The Court of Justice of the European Union in Luxembourg handed down a judgment in a compensation case involving a French man who claimed that a vaccination for hepatitis B caused his multiple sclerosis. The ruling specifies what type of evidence is allowed in EU member states in such cases, but it prompted a flurry of negative press coverage. [Nature News] Editorial

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

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Immunology (Oxford University)

NEW Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden (MIMS))

NEW Postdoctoral Position in Mucosal Immunology (Columbia University)

Full Professorship – Immunology (The Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Scientist – Immunogenomics (University of Oxford)

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)

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

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