Human Immunology News Volume 6.33 | Aug 21 2018

TOP STORY

Switchable CAR-T Cells Mediate Remission in Metastatic Pancreatic Ductal Adenocarcinoma

Switchable chimeric antigen receptor T (CAR-T) cells followed by administration of the switch directed against human epidermal growth factor receptor 2-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumor models. [Gut] Full Article

(Ranked by impact factor of the journal)

Epigenetic Dysregulation of Naive CD4⁺ T-Cell Activation Genes in Childhood Food Allergy

Using integrated DNA methylation and transcriptomic profiling, researchers found that polyclonal activation of naive CD4⁺ T cells through the T cell receptor resulted in poorer lymphoproliferative responses in children with immunoglobulin E-mediated food allergy. [Nat Commun] Full Article

Single-Cell Analysis Reveals that Stochasticity and Paracrine Signaling Control Interferon-Alpha Production by Plasmacytoid Dendritic Cells

Scientists report on a droplet-based microfluidic platform to investigate type I interferon (IFN) production in human plasmacytoid dendritic cells (pDCs) at the single-cell level. They showed that type I IFN but not tumor necrosis factor-α production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. [Nat Commun] Full Article

Baseline Cytokine Profiles of Tuberculin-Specific CD4⁺ T-Cells in Non-Muscle Invasive Bladder Cancer May Predict Outcomes of BCG Immunotherapy

Researchers examined the in vitro tuberculin-responsiveness of CD4⁺ T cells before Bacillus Calmette-Guérin (BCG) immunotherapy in 42 patients with high-risk non-muscle invasive bladder cancer. The frequencies and functionalities of cytokine-expressing CD4⁺ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. [Cancer Immunol Res] Abstract

Distinct HLA-E Peptide Complexes Modify Antibody-Driven Effector Functions of Adaptive NK Cells

The authors showed that adaptive natural killer (NK) cells discriminate differences between human leukocyte antigen E (HLA-E)-peptide complexes with exquisite specificity. Prolonged exposure to an environment displaying the HLA-E peptide ligand VMAPRTLFL, derived from the leader sequence of HLA-G, enriched adaptive NK cells with low FcεRγ expression, upregulated CD25 expression, increased proliferative activity, and resulted in elevated antibody-dependent cellular cytotoxicity and interferon-γ responses compared with other HLA-E peptide complexes. [Cell Rep] Full Article | Graphical Abstract

Pro-Inflammatory Effects of E-Cigarette Vapor Condensate on Human Alveolar Macrophages

Investigators compared the effect of unvaped e-cigarette liquid to e-cigarette vapor condensate (ECVC) on alveolar macrophage (AM) function. AMs were treated with ECVC and nicotine-free ECVC. AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species release and bacterial phagocytosis were assessed. [Thorax] Full Article | Press Release | Editorial

High-Dimensional Immune Phenotyping and Transcriptional Analyses Reveal Robust Recovery of Viable Human Immune and Epithelial Cells from Frozen Gastrointestinal Tissue

The authors provide a cryopreservation protocol allowing for storage of gastrointestinal tissue with preservation of viability and functionality of both immune and epithelial cells. [Mucosal Immunol] Abstract

Frequencies of Circulating Regulatory TIGIT⁺CD38⁺ Effector T Cells Correlate with the Course of Inflammatory Bowel Disease

Researchers determined whether regulatory and inflammatory phenotypes of circulating CD38⁺ effector T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric inflammatory bowel disease patients. [Mucosal Immunol] Abstract

IgM Response against Amyloid-Beta in Aging: A Potential Peripheral Protective Mechanism

Investigators examined the response of human monocyte-derived dendritic cells (DCs), T cells, and peripheral blood mononuclear cells from healthy aged and young subjects to amyloid-beta (Aβ) peptide 1-42, Aβ fibrils, and recombinant, nonaggregated tau-4 protein with a view to understand the role of peripheral immunity in Alzheimer’s disease. [Alzheimers Res Ther] Full Article

Biological Function of Eosinophil Extracellular Traps in Patients with Severe Eosinophilic Asthma

Scientists investigated the characteristics of eosinophil extracellular traps (EETs) from patients with non-severe asthma and severe eosinophilic asthma and evaluated EET function. [Exp Mol Med] Full Article

Human Lymph Nodes Maintain TCF-1^hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life

Researchers used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8⁺ T cells in lymph nodes, which maintain a distinct differentiation and functional profile compared with memory CD8⁺ T cells in blood, spleen, bone marrow, and lungs. [J Immunol] Abstract

Engineering of Primary Human B cells with CRISPR/Cas9 Targeted Nuclease

The authors report optimized CRISPR/Cas9 based genome engineering of primary human B cells. Their procedure involved enrichment of CD19⁺ B cells from peripheral blood mononuclear cells followed by activation, expansion, and electroporation of CRISPR/Cas9 reagents. [Sci Rep] Full Article

Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News.

Perivascular Macrophages in Health and Disease

Scientists examine the important functions of perivascular macrophages in various adult tissues and describe how these functions are perturbed in a broad array of pathological conditions. [Nat Rev Immunol] Abstract

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

RXi Pharmaceuticals and Karolinska Institutet Enter into Collaboration to Develop sd-rxRNA Compounds to Improve Functionality and Persistence of T Cells and NK Cells for the Advancement of Immuno-Oncology Therapeutics for Solid Tumors

RXi Pharmaceuticals Corporation announced that it has entered into a research collaboration with the Karolinska Institutet. This collaboration will explore RXi’s self-delivering RNAi (sd-rxRNA^®) compounds against targets involved in T cell and NK cell differentiation and/or in the immune cell tumor-induced stress response with the aim of producing anti-tumor adoptive cell therapy grafts with improved functionality and persistence. [RXi Pharmaceuticals Corporation] Press Release

Alberta Biotech Company Receives Canadian Government Funding for Immuno-Oncology Project

Edmonton’s General Intermediates of Canada Inc. announced that they have received conditional funding from the National Research Council of Canada Industrial Research Assistance Program related to their discovery of a new immuno-oncology compound that could play a role in the fight against cancer. [Edmonton’s General Intermediates of Canada Inc. (PR Newswire Association LLC.)] Press Release

Third Dosing Cohort to Be Initiated in MAGE-A4 SPEAR T-Cell Basket Study after Favorable Review of Safety from One Billion Cell Dose Cohort

Adaptimmune Therapeutics plc announced a favorable review of safety data from the second dose cohort of patients who received one billion transduced SPEAR T-cells targeting MAGE-A4 in the ongoing basket study in nine solid tumor indications. [Adaptimmune Therapeutics plc] Press Release

Viela Bio Announces Start of First Clinical Trial

Viela Bio announced the start of the company’s first clinical trial, a Phase I, first-in-human clinical trial of VIB9600, which is being developed for the treatment of adult patients with immune mediated diseases. [Viela Bio (PR Newswire Association LLC.)] Press Release

Immunocore Announces Start of Phase I ImmTAC^® Study in Patients with Solid Tumors

Immunocore Limited announced that it has dosed the first patient in a Phase I study, part of an ongoing collaboration with GlaxoSmithKline. [Immunocore Limited] Press Release

Singapore’s First Clinical Trial Approval for T Cell Engineered (TCR) Immunotherapy for Treatment of Liver Cancer

Lion TCR Pte. Ltd. received approval from Health Sciences Authority, Singapore, for its Phase I/II multicentre clinical study of its product candidate for treatment of relapsed liver cancer post-liver transplantation. [Lion TCR Pte. Ltd.] Press Release

Salk Institute Asks Judge to Narrow Scope of Gender-Discrimination Suit

Lawyers representing the Salk Institute for Biological Studies went to court, asking a judge to narrow the scope of a gender-discrimination lawsuit filed by molecular biologist Beverly Emerson. [Nature News] Editorial

Top Geneticist Loses £3.5-Million Grant in First Test of Landmark Bullying Policy

One of the world’s largest research-funding charities has revoked a £3.5-million (US$4.5-million) grant awarded to a top cancer geneticist, Nazneen Rahman, following allegations that she bullied scientists and other staff when she worked at the Institute of Cancer Research in London. [Nature News] Editorial

What Pakistan’s New Government Means for Science

Pakistan is reeling from a political earthquake — and researchers are both nervous and excited. The incoming administration promises to use science to alleviate poverty, but it is facing an imminent economic crisis. [Nature News] Editorial

The NIH Loosens Grip on Gene Therapy Trials

The directors of the National Institutes of Health (NIH) and the US FDA propose limiting the role of the NIH in assessing proposals for gene therapy experiments, the two explain in a commentary in the New England Journal of Medicine. [The Scientist] Editorial

NEW 30^th EORTC-NCI-AACR Symposium
November 13-16, 2018
Dublin, Ireland

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

NEW Postdoctoral Fellow – Cancer Therapeutics and Immunotherapy (Emory University)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Research Fellow – Neuropsychiatric Immunology (Cardiff University)

Faculty Position – Aging and the Immune System (Mayo Clinic)

Postdoctoral Position – Autoimmunity (Medical University of South Carolina)

Postdoctoral Fellow – Cancer Innate Immunity (Johnson & Johnson Pharmaceutical Research & Development)

Postdoctoral Scholar – Tumor Immunology and Immunotherapy (Northwestern University Feinberg School of Medicine)

Postdoctoral Position – DNA Damage Response and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Immunotherapy (California Institute for Biomedical Research)

Postdoctoral Fellowship Position – Innate Immunity and Neurodegeneration (The Mount Sinai Health System)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Postdoctoral Fellow – Immunoengineering for Muscle Regeneration (Duke University)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Human Immunology News? Click here to submit!

Comments or suggestions? Submit your feedback here.