Human Immunology News Volume 6.01 | Jan 9 2018

TOP STORY

Recurrent ECSIT Mutation Encoding V140A Triggers Hyperinflammation and Promotes Hemophagocytic Syndrome in Extranodal NK/T Cell Lymphoma

Through exome sequencing of extranodal natural killer/T cell lymphoma (ENKTL) tumor-normal samples, researchers identified a hotspot mutation in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene, encoding a V140A variant of ECSIT. In individuals with ENKTL, ECSIT-V140A was associated with activation of NF-κB, higher hemophagocytic syndrome incidence, and poor prognosis. [Nat Med] Abstract

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NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis

The authors used reflectance confocal microscopy imaging in humans and in mice to visualize tumor architecture in vivo. They demonstrated that signaling via the natural killer (NK) cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ secretion from intratumoral NK cells. [Immunity] Abstract | Graphical Abstract

Intravenous Delivery of Oncolytic Reovirus to Brain Tumor Patients Immunologically Primes for Subsequent Checkpoint Blockade

Scientists showed, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human Orthoreovirus (reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. [Sci Transl Med] Abstract | Press Release

TNF Blockade Induces a Dysregulated Type I Interferon Response without Autoimmunity in Paradoxical Psoriasis

Investigators showed that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells, and reduced T-cell numbers, when compared to classical psoriasis. [Nat Commun] Full Article

Human Macrophages Differentially Produce Specific Resolvin or Leukotriene Signals that Depend on Bacterial Pathogenicity

Scientists showed that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. Escherichia coli and Staphylococcus aureus each stimulated predominantly proinflammatory 5-lipoxygenase and cyclooxygenase pathways in M1 macrophages. [Nat Commun] Full Article

p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer after Treatment with a p53 Vaccine and Gemcitabine Chemotherapy

Investigators conducted a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. Enhanced in vitro recognition of p53 peptides was detectable after immunization in both the CD4⁺ and CD8⁺ T cell compartments in 5/11 and 6/11 patients, respectively. [Clin Cancer Res] Abstract

Soluble SLAMF6 Receptor Induces Strong CD8⁺ T Cell Effector Function and Improves Anti-Melanoma Activity In Vivo

Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, researchers found that seSLAMF6 reduced activation-induced cell death and had an anti-apoptotic effect on tumor infiltrating lymphocytes. CD8⁺ T cells costimulated with seSLAMF6 secreted more interferon gamma and displayed augmented cytolytic activity. [Cancer Immunol Res] Abstract

Expandable Arterial Endothelial Precursors from Human CD34⁺ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition

The authors found that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34⁺ cells found in umbilical cord blood or adult bone marrow. [Stem Cell Reports] Full Article

The Act1 D10N Missense Variant Impairs CD40 Signaling in Human B-Cells

As assessed by flow cytometry, Act1 protein was expressed at the highest levels in monocytes, with lower levels in T-cells and B-cells. However, monocytes, T-cells and B-cells failed to respond to IL-17A stimulation of PBMCs, as measured by flow cytometric determination of NF-κB phospho-p65. [Genes Immun] Abstract

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The Dawn of Vaccines for Cancer Prevention

An important role of the immune system is in the surveillance for abnormal or transformed cells, which is known as cancer immunosurveillance. Through this process, the first changes to normal tissue homeostasis caused by infectious or other inflammatory insults can be detected by the immune system through the recognition of antigenic molecules (including tumor antigens) expressed by abnormal cells. [Nat Rev Immunol] Abstract

Concise Review: Human Pluripotent Stem Cells to Produce Cell-Based Cancer Immunotherapy

Human pluripotent stem cells (PSCs) provide a promising resource to produce immune cells for adoptive cellular immunotherapy to better treat and potentially cure otherwise lethal cancers. Cytotoxic T cells and natural killer cells can now be routinely produced from human PSCs. [Stem Cells] Full Article

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Adaptive Biotechnologies Announces Partnership with Microsoft to Decode the Human Immune System to Improve the Diagnosis of Disease

Adaptive Biotechnologies announced their partnership with Microsoft to map the genetics of the human immune system, or immunome, in order to detect cancers and other diseases in their earliest stage, when they can be more effectively treated. [Adaptive Biotechnologies] Press Release

Lycera Announces Initiation of Phase Ib Study of Novel Immuno-Oncology Candidate LYC-55716 in Combination with Pembrolizumab

Lycera Corp. announced the initiation of a Phase Ib clinical trial of the company’s novel immuno-oncology therapeutic candidate, LYC-55716, in combination with pembrolizumab. LYC-55716 is a first-in-class oral, selective retinoic acid-related orphan receptor-gamma agonist designed to reprogram the immune system in patients with solid tumors. [Lycera Corp.] Press Release

Feinstein Institute Researcher Awarded $1.2M to Continue Sepsis Research

Professor Haichao Wang, PhD, received a $1.2 million grant from the National Institutes of Health’s National Institute for General Medical Sciences to continue his search to identify different proteins associated with sepsis, which could lead to a targeted treatment for the condition. [Feinstein Institute for Medical Research] Press Release

Bicycle Therapeutics Secures an Innovate UK Grant to Develop the Next Generation of Antibiotics

Bicycle Therapeutics announced that it has been awarded a grant from Innovate UK to apply Bicycle technology to develop the next generation of novel antibiotics. [Bicycle Therapeutics] Press Release

Evelo Biosciences Announces Issuance of U.S. Patent Supporting Monoclonal Microbial Oncology Trials

Evelo announced that the U.S. Patent and Trademark Office has issued U.S. Patent No. 9,855,302 covering Bifidobacteria for the treatment of cancer in combination with checkpoint inhibitors. [Evelo Biosciences (PR Newswire Association LLC.)] Press Release

CGT Catapult Announces Vector Production Agreement with Adaptimmune

The Cell and Gene Therapy (CGT) Catapult announced it has signed an agreement with Adaptimmune for vector production at CGT Catapult’s UK based GMP manufacturing centre. The agreement will ensure vector supply production for Adaptimmune’s ongoing studies with all three SPEAR T-cell therapies, MAGE-A4, MAGE-A10 and AFP. [The Cell and Gene Therapy Catapult] Press Release

Koch-Backed Groups Urge Congress to Pass Right-to-Try Legislation

Several deep-pocketed political advocacy groups founded by Charles and David Koch are ramping up their advocacy before Congress on a niche issue: access to experimental drugs. [STAT News] Editorial

Germany vs Elsevier: Universities Win Temporary Journal Access after Refusing to Pay Fees

The Dutch publishing giant Elsevier has granted uninterrupted access to its paywalled journals for researchers at around 200 German universities and research institutes that had refused to renew their individual subscriptions at the end of 2017. [Nature News] Editorial

NEW Gordon Research Conferences: Biology of Acute Respiratory Infection
March 18-23, 2018
Ventura, California, United States

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NEW Postdoctoral Position – Microbiology and Immunology (University of Maryland)

NEW Biologist – Immunology (Eli Lilly and Company)

NEW Head of Laboratory – Cancer Vaccines/Oncolytic Viruses (Boehringer Ingelheim)

Scientist – Immunology (STEMCELL Technologies Inc.)

Investigator – Immuno-Oncology (Bristol-Myers Squibb)

Scientist – Immuno-Oncology (Bristol-Myers Squibb)

Postdoctoral Fellow – Immune Surveillance (University of Massachusetts)

Postdoctoral Research Associate – Human Immunology (Benaroya Research Institute at Virginia Mason)

Postdoctoral Positions – Immunotherapy (University of Houston)

PhD Candidate – Innate Immunity in Lung Adenocarcinoma (Helmholtz Zentrum München)

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