Human Immunology News Volume 6.24 | Jun 19 2018

TOP STORY

Inflamed Neutrophils Sequestered at Entrapped Tumor Cells via Chemotactic Confinement Promote Tumor Cell Extravasation

To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, researchers employed a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell-cell interactions. [Proc Natl Acad Sci USA] Abstract

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Age-Related Decline in Primary CD8⁺ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8⁺ T Cells

Researchers showed that “virtual memory” T cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells retain proliferative capacity in both aged mice and humans. [Cell Rep] Full Article | Graphical Abstract

Notch Signaling Facilitates In Vitro Generation of Cross-Presenting Classical Dendritic Cells

Co-culture with OP9 stromal cells expressing the Notch ligand Delta-like 1 greatly increased the yield of IRF8-dependent CD141⁺ classical dendritic cells from human bone marrow progenitors cultured with FLT3 ligand. [Cell Rep] Full Article | Graphical Abstract

Synergistic Activation of Pro-Inflammatory Type-2 CD8⁺ T Lymphocytes by Lipid Mediators in Severe Eosinophilic Asthma

In two independent cohorts the authors showed that, in contrast to Th2 cells, type-2 cytokine-secreting CD8⁺CRTH2⁺ cells are enriched in blood and airways in severe eosinophilic asthma. [Mucosal Immunol] Abstract

Autologous CD19-Targeted CAR T Cells in Patients with Residual CLL following Initial Purine Analog-Based Therapy

Investigators report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 as a consolidative therapy in eight patients with residual chronic lymphocytic leukemia (CLL) following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab. [Mol Ther] Abstract | Graphical Abstract

Inducing CCR5Δ32/Δ32 Homozygotes in the Human Jurkat CD4⁺ Cell Line and Primary CD4⁺ Cells by CRISPR-Cas9 Genome-Editing Technology

Designing a pair of single-guide RNA targeting the flank region of the CCR5Δ32 mutation locus, scientists applied the CRISPR-Cas9 and lentiviral packaging system to successfully convert wild-type C-C chemokine receptor type 5 (CCR5) into CCR5Δ32/Δ32 homozygotes in the human Jurkat CD4⁺ cell line and primary CD4⁺ cells, exactly the same as the naturally occurring CCR5Δ32/Δ32 mutation. [Mol Ther Nucleic Acids] Full Article

Flagellin Is a Th1 Polarizing Factor for Human CD4⁺ T Cells and Induces Protection in a Murine Neonatal Vaccination Model of Rotavirus Infection

The authors found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4⁺ T cells were activated in the presence of flagellin, there was high level of expression of IFN-γ in both neonates and adults. [Vaccine] Abstract

Prognostic Value of Intra-Tumoral CD8⁺/FoxP3⁺ Lymphocyte Ratio in Patients with Resected Colorectal Cancer Liver Metastasis

Investigators studied the spatial distribution and prognostic role of tumor-infiltrating CD8⁺ cytotoxic T-cells and FoxP3⁺ regulatory T-cells at the metastatic site of colorectal-cancer-liver-metastases patients. [J Surg Oncol] Full Article

CD46 Is a Potent Co-Stimulatory Receptor for Expansion of Human IFN-γ-Producing CD8⁺ T Cells

Researchers demonstrated that CD46 co-stimulation induced secretion of IFN-γ as well as expansion of IFN-γ-secreting CD8⁺ T cells. In contrast to CD46 co-stimulation of CD4⁺ T cells, CD8⁺ T cells did not differentiate into a regulatory IL-10-secreting phenotype. [Immunol Lett] Abstract

Common Gamma Chain Cytokines Promote Regulatory T Cell Development and Survival at the CD4⁺CD8⁺ Stage in the Human Thymus

Scientists showed that interleukin-2 promotes the development of FOXP3⁺ thymocytes and enhances their survival at the double positive (DP) phase. IL-2 increased the frequency of FOXP3⁺ cells and promoted the Treg phenotype after TCR-mediated positive selection at the most mature DP stage. [Scand J Immunol] Abstract

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The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions

The autoimmune lymphoproliferative syndrome (ALPS)-FAS was the first description of a monogenic cause of autoimmunity, but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The recognition of these genetic diseases brought new information on the role of this apoptotic pathway in controlling the adaptive immune response in humans. [J Clin Immunol] Abstract

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Ziopharm Oncology Reports on Status of Investigational New Drug Application for Phase I Trial to Evaluate CD19-Targeted CAR T Therapy

Ziopharm Oncology, Inc. announced the FDA placed on clinical hold a Phase I trial to evaluate CD19-specific CAR-T therapies manufactured under point-of-care and requested additional information in support of the investigational new drug application for the trial. [Ziopharm Oncology, Inc.] Press Release

CStone Pharmaceuticals Initiates Two Pivotal Phase II Studies of the Anti-PD-L1 Monoclonal Antibody CS1001

CStone Pharmaceuticals announced that two pivotal Phase II studies exploring the efficacy and safety of CS1001 in patients with natural killer cell/T-cell lymphoma and classical Hodgkin’s lymphoma have been initiated, and have respectively enrolled and dosed the first patient. [CStone Pharmaceuticals (PR Newswire Association LLC.)] Press Release

Seattle Children’s Opens Immunotherapy Trial for Children with Relapsed Central Nervous System Tumors that Delivers CAR T Cells Directly into the Brain

Seattle Children’s has opened a pioneering chimeric antigen receptor (CAR) T-cell immunotherapy trial for children and young adults with relapsed or refractory HER2-positive central nervous system tumors where CAR T cells will be delivered directly into the brain. [Seattle Children’s Hospital] Press Release

U.S. Legislators Back Larger Facilities Budget for NSF

The National Science Foundation (NSF) in Alexandria, Virginia, is in line for a budget increase of 4% to 5% next year. That assessment is based on bills approved recently by the spending committees in both chambers of Congress. Lawmakers have also signaled support for growing the account that NSF uses to build major new scientific facilities. [ScienceInsider] Editorial

Why the Medical Research Grant System Could Be Costing Us Great Ideas

The medical research grant system in the United States, run through the National Institutes of Health, is intended to fund work that spurs innovation and fosters research careers. In many ways, it may be failing. [The New York Times] Editorial

House Bill Gives NIH a 3% Boost in 2019, to $38.3 Billion

A draft bill released by a House of Representatives spending panel would give the National Institutes of Health (NIH) in Bethesda, Maryland, a $1.25 billion raise in 2019, to $38.3 billion. That is 3% more than this year’s level and $4.1 billion more than President Donald Trump’s administration had requested. [ScienceInsider] Editorial

NEW European CanCer Organisation (ECCO) 2018: European Cancer Summit
September 7-9, 2018
Vienna, Austria

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NEW Associate Professor or Senior Scientist – Immunological Methods and Immune System of Production Animals (Aarhus University)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Postdoctoral Fellow – Immunoengineering for Muscle Regeneration (Duke University)

PhD Student Positions – Immunology (Multiple Locations)

Research Officer – Immunology (The Walter and Eliza Hall Institute of Medical Research)

PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

Postdoctoral Fellow – Immunology (Boston University School of Medicine)

Postdoctoral Fellow – Innate Immune Signaling (Houston Methodist Research Institute)

PhD Student – Cancer Immunology (German Cancer Research Center)

Postdoctoral Researcher Positions – Rapid Identification of Autoantigens in Autoimmune Disease (BioMed X Innovation Center)

PhD Student – Immunology of Cell Death & Cancer Immunotherapy (KU Leuven)

Scientist/Senior Scientist – Lentivirus Production (Obsidian Therapeutics)

Scientist/Senior Scientist – Bioinformatics and Data Sciences (Obsidian Therapeutics)

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