Human Immunology News Volume 5.32 | Aug 15 2017

TOP STORY

Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade

Researchers utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses revealed a spectrum of tumor-infiltrating T cell populations that were highly similar between tumor models and indicated that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF

Scientists used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription-factor binding, and gene expression in interferon (IFN)-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an “M2”-like homeostatic and reparative phenotype. [Immunity] Abstract | Graphical Abstract

Monocytes Inhibit Hepatitis C Virus-Induced TRAIL Expression on CD56^bright NK Cells

The authors had previously shown that cell-culture-derived HCV (HCVcc) enhanced tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) expression on healthy but not on HCV-infected patient-derived natural killer (NK) cells, which was likely dependent on accessory cells. Here, they sought mechanistic insights involved in altered TRAIL upregulation in this setting. [J Hepatol] Abstract | Graphical Abstract

Discovery of Novel Drug Sensitivities in T-PLL by High-Throughput Ex Vivo Drug Testing and Mutation Profiling

Investigators systematically explored the diversity of drug responses in T-cell prolymphocytic leukemia (T-PLL) patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. All T-PLL samples were sensitive to the CDK inhibitor SNS-032, which overcame stromal-cell mediated protection and elicited robust p53-activation and apoptosis. [Leukemia] Abstract

Comprehensive miRNA Expression Profiling in Human T-Cell Acute Lymphoblastic Leukemia by Small RNA-Sequencing

Researchers applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-cell acute lymphoblastic leukemia (T-ALL) patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. This analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background. [Sci Rep] Full Article

Genetic Variation at the CD28 Locus and Its Impact on Expansion of Pro-Inflammatory CD28 Negative T Cells in Healthy Individuals

The authors assessed whether the primary sclerosing cholangitis (PSC)-associated CD28 risk variant A affects CD28 expression and T cell function in healthy individuals. Homozygotes for the PSC disease risk allele showed significantly lower CD28 mRNA expression ex vivo than either GG or AG in total peripheral blood mononuclear cells. [Sci Rep] Full Article

Proliferative Capacity Exhibited by Human Liver-Resident CD49a⁺CD25⁺ NK Cells

Scientists conducted a prospective dual-center cross-sectional study in patients undergoing liver transplantation or tumor-free liver resections, in which both liver tissue and peripheral blood samples were obtained from each consenting study participants. Their results showed that, within cirrhotic liver samples, intrahepatic natural killer (NK) cells were particularly enriched for CD49a⁺ NK cells when compared to tumor-free liver resection samples. [PLoS One] Full Article

Photochemical Inactivation of Lymphocytes by Riboflavin with Visible Light for TA-GvHD Prevention

Researchers focused on the photochemical effects of riboflavin excited by visible light (RB + L) treatment on human lymphocytes, to study the feasibility of using RB + L treatment to prevent adverse immune reactions caused by transfused lymphocytes. Results showed that γ-irradiation and RB + L treated cells showed a decline in cell viability. [J Photochem Photobiol B] Abstract

Human Blood T_fr Cells Are Indicators of Ongoing Humoral Activity Not Fully Licensed with Suppressive Function

Investigators found that blood T follicular regulatory (T_fr) cells are increased in Sjögren syndrome, an autoimmune disease with ongoing germinal center reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination. [Sci Immunol] Full Article

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Humanized Mouse Models to Study Human Cell-Mediated and Humoral Responses to Dengue Virus

The author discusses advances in the development of humanized animal models and highlights how they could be used for antiviral and dengue vaccine testing if limitations with cell-mediated immunity and seroconversion to IgG were overcame. [Curr Opin Virol] Abstract

Markers of T Cell Senescence in Humans

Researchers focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. They look at the implications that senescent T cells could have on human health and diseases. They discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers. [Int J Mol Sci] Full Article

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

CARsgen Launches First-in-Class Anti-Claudin18.2 CAR-T Clinical Trial

CARsgen Therapeutics announced its first-in-class anti-Claudin18.2-CAR-T cell therapy for gastric and pancreatic cancers has entered into a Phase I clinical trial and started patient recruitment at the Changhai Hospital of Shanghai. [CARsgen Therapeutics (PR Newswire Association LLC.)] Press Release

InDex Pharmaceuticals Receives Orphan-Drug Designation for Pediatric Ulcerative Colitis in the US

InDex Pharmaceuticals Holding AB announced that the FDA has granted orphan-drug designation for the drug candidate cobitolimod for treatment of ulcerative colitis in pediatric patients. [InDex Pharmaceuticals Holding AB] Press Release

Budget Cuts Fuel Frustration among Japan’s Academics

Japan’s premier scientific research institution, RIKEN, turned 100 this year, and celebrated with a grand ceremony attended by the empress and emperor. But not everybody was in the mood to party. In the old days, RIKEN was known as a paradise for scientists because of its generous funding. No longer: as Japan cuts off funds in the face of continuing financial uncertainty, the cracks are starting to show. [Nature News] Editorial

New FDA Security Rules Will Bar Agency from Hiring Some Foreign Nationals

The FDA is moving to adopt a new policy on security background checks that is sowing confusion and alarm among some of its scientists. The change, described in a “communications plan” shared with the agency’s senior staff in recent weeks, appears to effectively bar the agency from hiring—as employees or contractors—foreign nationals who have not lived in the United States for a total of three out of the last five years. [ScienceInsider] Editorial

NEW Cell-Weizmann Institute of Science Symposium: Next Gen Immunology
February 11-14, 2018
Rehovot, Israel

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NEW Protein Engineering Scientists – Oncology, Autoimmune and Infectious Diseases (Immunocore)

NEW Postdoctoral Scholar – Regulation of Immune Responses (University of Iowa)

Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

Postdoctoral Research Fellow – Immunology (Harvard Medical School, Joslin Diabetes Center)

Postdoctoral Researcher – Inflammatory Diseases (University of Pennsylvania)

Assistant Professor – Cell Science (University of Manitoba)

Postdoctoral Research Associate – Autoimmune Disease Research (Benaroya Research Institute at Virginia Mason)

Postdoctoral Fellow – B Cells in Autoimmune Diseases (Inserm)

Postdoctoral Position – Molecular Biology and Immunology (Harvard Medical School)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

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

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Assistant, Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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