Human Immunology News Volume 4.46 | Nov 22 2016

TOP STORY

Epigenomic Profiling of Human CD4⁺ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Researchers generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA⁺ CD4⁺ memory T (Tmem) cells from blood and CD69⁺ Tmem cells from bone marrow. [Immunity] Full Article | Graphical Abstract

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17q21 Asthma-Risk Variants Switch CTCF Binding and Regulate IL-2 Production by T Cells

Researchers found several 17q21 variants overlapped enhancers present mainly in primary immune cell types. CD4⁺ T cells showed the greatest increase in ORMDL3 expression in individuals carrying the asthma-risk alleles, where ORMDL3 negatively regulated interleukin-2 production. [Nat Commun] Full Article

Dendritic Cell-Elicited B-Cell Activation Fosters Immune Privilege via IL-10 Signals in Hepatocellular Carcinoma

Scientists established that over 50% B cells in hepatocellular carcinoma exhibit an FcγRII^low/− activated phenotype, and high infiltration of these cells positively correlates with cancer progression. [Nat Commun] Full Article

B Cell Depleting Therapy Regulates Splenic and Circulating T Follicular Helper Cells in Immune Thrombocytopenia

To determine the effect of B cell depletion on human T follicular helper cells (TFH), scientists quantified B cells and TFH in the spleen and in the blood from immune thrombocytopenia patients treated or not with rituximab. They showed that B cell depletion led to a dramatic decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly produced by TFH. [J Autoimmun] Abstract

A Novel Xenogeneic Graft-versus-Host Disease Model for Investigating the Pathological Role of Human CD4⁺ or CD8⁺ T Cells Using Immunodeficient NOG Mice

The authors established two novel xenogeneic-graft-versus-host disease models. Human CD4⁺ or CD8⁺ T cells were purified from peripheral blood and were transplanted into immunodeficient NOD/Shi-scid IL2rg^null (NOG) mice. [Am J Transplant] Abstract

Endotoxemia Contributes to CD27⁺ Memory B-Cell Apoptosis via Enhanced Sensitivity to Fas Ligation in Patients with Cirrhosis

Using isolated naïve and memory B-cells from patients with cirrhosis and age-matched controls, ex vivo and activation-induced sensitivity to Fas-mediated apoptosis was assessed under relevant experimental conditions. [Sci Rep] Full Article

Roles of Calpain-Calpastatin System (CCS) in Human T Cell Activation

The authors showed that CCS genes are constitutively expressed, and that both calpains are constitutively active in resting, circulating human CD4⁺ and CD8⁺ lymphocytes. [Oncotarget] Full Article

An NK Cell Line (haNK) Expressing High Levels of Granzyme and Engineered to Express the High Affinity CD16 Allele

Researchers showed high levels of granzyme in haNK cells, and demonstrated the effects of irradiation of haNK cells on multiple phenotypic markers, viability, IL-2 production, and lysis of a spectrum of human tumor cells. [Oncotarget] Full Article | Press Release

Human B-Cell Memory Is Shaped by Age- and Tissue-Specific T-Independent and GC-Dependent Events

Investigators showed that, whereas switched memory B cells are mostly generated in the germinal centers at all ages, IgM memory B cells can be distinct in three types with different developmental history. Innate IgM memory B cells, the largest pool in infants, are generated in the spleen by a germinal center-independent mechanism. [Eur J Immunol] Abstract

Role of Dendritic Cell Maturation Factors Produced by Human Invariant NKT Cells in Immune Tolerance

Researchers used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4⁺ iNKT cells. S100A8 had a strong maturation effect. [J Leukoc Biol] Abstract

Pregnancy Persistently Affects Memory T Cell Populations

Investigators aimed to show the short term and the long term effects of pregnancy on the constitution, size and activation status of peripheral human memory T-lymphocyte populations. Effector memory and central memory T-lymphocytes were analyzed using flow cytometry of peripheral blood from 14 nulligravid, 12 primigravid and 15 parous women that were on average 18 months postpartum. [J Reprod Immunol] Abstract | Full Article

Partial Exhaustion of CD8 T Cells and Clinical Response to Teplizumab in New-Onset Type 1 Diabetes

Researchers identified a population of CD8 T cells that accumulated in patients with the best response to treatment and showed that these cells phenotypically resembled exhausted T cells by expressing high levels of the transcription factor EOMES, effector molecules, and multiple inhibitory receptors, including TIGIT and KLRG1. [Sci Immunol] Abstract

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Development of T Follicular Helper Cells and Their Role in Disease and Immune System

The biology of T follicular helper cells, including their differentiation and transcriptional regulation will be described in the present review. Some of the developments of these cells in immunodeficiency diseases, autoimmunity and cancer will also be taken into account. [Biomed Pharmacother] Abstract

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

Inovio’s Cancer Immunotherapy (INO-3112) Generates T Cell Immune Responses in Tumor Tissue and Peripheral Blood in Patients with HPV-Associated Head and Neck Cancer

Inovio Pharmaceuticals, Inc. announced an interim data analysis showing that its INO-3112 cancer immunotherapy product generated antigen-specific CD8⁺ killer T cell responses measured both in tumor tissue and in peripheral blood from subjects with head and neck cancer associated with human papillomavirus (HPV). [Inovio Pharmaceuticals, Inc.] Press Release

Tiziana Life Sciences Announces New Data with Foralumab, a Fully Human Anti-CD3 Antibody Being Developed as an Oral Therapy for NASH and Autoimmune Diseases

Tiziana Life Sciences plc announced new data from animal studies demonstrating the potential of its novel oral therapy with foralumab for NASH, diabetes and other life-threatening inflammatory diseases. Tiziana’s foralumab is the only fully human engineered anti-CD3 monoclonal antibody in clinical development to date. [Tiziana Life Sciences plc] Press Release

Bellicum Pharmaceuticals Recommended for $16.9 Million Award from the Cancer Prevention and Research Institute of Texas

Bellicum Pharmaceuticals, Inc. announced that the company received notice of a Product Development award totaling approximately $16.9 million from the Cancer Prevention and Research Institute of Texas to support clinical studies of its lead product candidate BPX-501. [Bellicum Pharmaceuticals, Inc.] Press Release

Celyad Announces the Approval to Initiate its NKR-2 CAR-T Clinical Trial in Belgium

Celyad announced the approval in Belgium to initiate the THINK clinical trial. THINK is the second clinical trial of its NKR-2 product candidate, a CAR-T cell therapy using NKG2D ligands as a target, to evaluate safety and efficacy in seven cancer indications including both solid and hematological malignancies. [Celyad] Press Release

CEL-SCI Submits Response to FDA in Connection with Partial Clinical Hold on Phase III Clinical Trial

CEL-SCI Corporation announced that it has submitted its response to the U.S. Food and Drug Administration (FDA) regarding the previously announced partial clinical hold of CEL-SCI’s Phase III clinical trial of its investigational drug Multikine in patients with squamous cell carcinoma of the head and neck. [CEL-SCI Corporation] Press Release

NW Bio Announces Phase II Clinical Trial Program Combining DCVax^®-L and Pembrolizumab (Keytruda^®) for Colorectal Cancer

Northwest Biotherapeutics joined the University Medical Center of the Johannes Gutenberg University Mainz in Germany in announcing a Phase II clinical trial program combining DCVax^®-L and Pembrolizumab for colorectal cancer with liver metastases. [Northwest Biotherapeutics, Inc.] Press Release

Immigrant and Minority Scientists Shaken by Trump Win

Scientists are reconsidering whether to work or study in the United States. Worries include job prospects, discrimination—and safety. [Nature News] Editorial

Peer-Review ‘Heroes’ Do Lion’s Share of the Work

In 2015, the number of scientists in the life sciences far exceeded the demand on them for peer review, according to Michail Kovanis, a computational physicist at the French National Institute of Health and Medical Research in Paris, and his colleagues. Yet their study also suggests – based on data obtained from a rapidly-growing website of peer-review activity – that 20% of the scientists undertook between 69% and 94% of reviews last year, lending credence to some researchers’ complaints that they are overburdened. [Nature News] Editorial

Cautious Welcome for UK’s Vague £2 Billion Research Pledge

UK scientists have welcomed a surprise government promise to invest an extra £2 billion (US$2.5 billion) per year into research and development by 2020 – although details of the pledge will not be made clear for at least another two days. [Nature News] Editorial

Conservatives, Liberals Team Up against Animal Research

“Painful, bizarre, and wasteful experiments.” Buying dogs “just to cut them apart … and kill them.” These statements might sound like the rhetoric used by extreme animal rights groups, but they come from White Coat Waste—a new, unlikely coalition of fiscal conservatives and liberal activists that aims to end federal funding for research involving dogs and other animals by targeting people’s pocketbooks in addition to their heartstrings. [ScienceInsider] Editorial

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