Volume 3.43 | Nov 3

Human Immunology News 3.43 November 3, 2015
Human Immunology News
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Immunogenicity of Somatic Mutations in Human Gastrointestinal Cancers
Using a next-generation sequencing approach combined with high-throughput immunologic screening, scientists demonstrated that tumor-infiltrating lymphocytes from nine out of ten patients with metastatic gastrointestinal cancers contained CD4+ and/or CD8+ T cells that recognized one to three neo-epitopes derived from somatic mutations expressed by the patient’s own tumor. [Science] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Cancer Mediates Effector T Cell Dysfunction by Targeting MicroRNAs and EZH2 via Glycolysis Restriction
Researchers found that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. [Nat Immunol] Abstract | Press Release

Human Caspase-4 and Caspase-5 Regulate the One-Step Non-Canonical Inflammasome Activation in Monocytes
The authors report that caspase-4 and caspase-5 mediate IL-1α and IL-1β release from human monocytes after lipopolysaccharide stimulation. [Nat Commun] Full Article

Crohn’s Disease-Derived Monocytes Fail to Induce Paneth Cell Defensins
Using cultures of human ileal tissue, investigators showed that the secretome of peripheral blood mononuclear cells from healthy controls restored the attenuated Paneth cell α-defensin expression characteristic of patients with ileal Crohn’s disease. [Proc Natl Acad Sci USA] Abstract | Full Article

Ubiquitin-Dependent Endocytosis of NKG2D-DAP10 Receptor Complexes Activates Signaling and Functions in Human NK Cells
In experiments with human NK cells and cell lines, researchers found that the ligand-induced endocytosis of NK receptor group 2, member D (NKG2D)-DNAX-activating protein 10 (DAP10) depended on the ubiquitylation of DAP10, which was also required for degradation of the internalized complexes. [Sci Signal] Abstract

Impact of the Inflammatory Microenvironment on T-Cell Phenotype in the Progression from Reflux Esophagitis to Barrett Esophagus and Esophageal Adenocarcinoma
Previous studies have examined the secreted cytokines from esophageal tissue during disease progression but this study is the first to examine the activation phenotype and the inflammatory profile of CD4+ and CD8+ T-cells in human esophagitis, Barrett esophagus and esophageal adenocarcinoma tissue. [Cancer Lett] Abstract

Interferon Gamma Boosts the Nucleotide Oligomerization Domain 2-Mediated Signaling Pathway in Human Dendritic Cells in an X-Linked Inhibitor of Apoptosis Protein and Mammalian Target of Rapamycin-Dependent Manner
Because the simultaneous presence of various microbial products and cytokines in inflamed tissues modulates dendritic cell (DC) function, scientists examined how interferon gamma, a central modulator of inflammation, affects the nucleotide oligomerization domain 2-mediated signaling pathway in human conventional DCs. [Cell Mol Immunol] Abstract

Enhancement of Regulatory T Cell-Like Suppressive Function in MT-2 by Long-Term and Low-Dose Exposure to Asbestos
The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the human T-lymphotropic virus-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. [Toxicology] Abstract

Rhinovirus Stimulated IFN-α Production: How Important Are Plasmacytoid DCs, Monocytes and Endosomal pH?
Investigators demonstrated that, using intracellular flow cytometry, >90% of the IFN-α-producing cells in human blood mononuclear cells following human rhinovirus 16 exposure are plasmacytoid dendritic cells, whereas monocytes and myeloid dendritic cells contribute only 10% and <1%, respectively, of the IFN-α production. [Clin Transl Immunol] Full Article

Expression Analysis of Surface Molecules on Human Thymic Dendritic Cells with the 10th HLDA Workshop Antibody Panel
Scientists studied the binding of 71 monoclonal antibodies submitted to the HLDA10 workshop to human CD123+ plasmacytoid dendritic cells (DC) and the two subsets of conventional DC isolated from thymus tissue of infants undergoing corrective heart surgery. [Clin Transl Immunol] Full Article

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Regulatory T Cells in Cardiovascular Diseases
The authors provide an overview of the roles of regulatory T cells in the pathogenesis of a number of cardiovascular diseases, including atherosclerosis, hypertension, ischemic stroke, abdominal aortic aneurysm, Kawasaki disease, pulmonary arterial hypertension, myocardial infarction and remodeling, postischemic neovascularization, myocarditis and dilated cardiomyopathy, and heart failure. [Nat Rev Cardiol] Abstract

Peptide Vaccines in Breast Cancer: The Immunological Basis for Clinical Response
The authors discuss peptide-based vaccines in breast cancer, immune responses and clinical outcomes, which include studies on animal models and Phase I, Phase I/II, Phase II and Phase III clinical trials. [Biotechnol Adv] Abstract

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Phase IIa Results from CAR-T CD20 Immuno-Oncology Clinical Development Program for Advanced B-Cell Non-Hodgkin Lymphoma
Cellular Biomedicine Group Inc. announced results from an ongoing Phase IIa clinical trial evaluating the safety, feasibility and anti-tumor activity of its acquired chimeric antigen receptor-modified T-cells (CAR-T) immunotherapy targeting CD20 for the treatment of patients with advanced B-cell non-Hodgkin lymphoma. [Press release from Cellular Biomedicine Group Inc. discussing research presented at the 4th International Conference on Translational Medicine, Baltimore] Press Release

Adaptimmune Announces Upcoming Data Presentation
Adaptimmune announced that it will present new data from trials of its NY-ESO affinity enhanced T-cell therapy in patients with synovial sarcoma and myeloma, as well as data from preclinical safety assessments of its affinity enhanced T-cell therapy directed at MAGE A-10. [Press release from Adaptimmune Therapeutics plc discussing research to be presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC), National Harbor] Press Release

Biothera to Present Three Abstracts at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
Biothera’s Imprime PGG, a safe and systemically administered pathogen associated molecular pattern, initiates an integrated immune response with the potential to dramatically boosts the efficacy of checkpoint inhibitors and other anti-tumor monoclonal antibodies for cancer cell killing and long-term disease control. [Press release from Biothera, The Immune Health Company discussing research to be presented at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston] Press Release

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Sanofi and BioNTech Announce Cancer Immunotherapy Collaboration and License Agreement
The research collaboration between Sanofi and BioNTech will leverage the scientific expertise of the two organizations to discover and develop up to five cancer immunotherapies, each consisting of a mixture of synthetic messenger RNAs. [BioNTech A.G.] Press Release

GSK and Merck to Study Immunotherapy Combination as Potential Cancer Treatment
GSK and Merck announced the initiation of a Phase I clinical trial designed to evaluate GSK’s investigational immunotherapy GSK3174998 as monotherapy and in combination with Merck’s anti-PD-1 therapy, Keytruda® in patients with locally advanced, recurrent or metastatic solid tumor(s) that have progressed after standard treatment. [GlaxoSmithKline plc] Press Release

TxCell Secures Key CAR-Treg Patent through Exclusive Option Agreement with Yeda, the Commercial Arm of World’s Recognized Weizmann Institute of Science
Resulting from the exclusive option agreement, TxCell will gain exclusive access to a CAR-Treg patent for suppression of autoimmune and inflammatory diseases originated in the Weizmann Institute of Science laboratory of Professor Zelig Eshhar. [TxCell SA] Press Release

New Immunotherapy Treatment May Clear Cancer-Causing HPV Infections Faster
A new therapeutic vaccine, GTL001, developed by Genticel to clear human papillomavirus (HPV) strains 16 and 18 – the types most likely to cause cancer – is being evaluated for safety in a Phase I clinical trial at the University of Louisville. [University of Louisville] Press Release

Completion of Phase I Clinical Trial of Novel Syk Inhibitor HMPL-523 for Autoimmune Diseases in Healthy Volunteers
Hutchison China MediTech Limited announced that Hutchison MediPharma Limited, its drug R&D subsidiary, has successfully completed its first-in-human Phase I clinical trial of HMPL-523. HMPL-523 is a novel, highly selective and potent small molecule inhibitor targeting spleen tyrosine kinase, also known as Syk, a key component in B-cell receptor signaling. [Hutchison China MediTech Limited] Press Release
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Therapeutic Goods Administration (Australia)
NEW 2016 Advanced Immunohematology & Molecular (AIM) Symposium
June 5-6, 2016
Houston, United States

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NEW Professor – Biomedical Science (The Institute of Basic Medical Sciences Chinese Academy of Medical Sciences)

NEW Assistant Professor – Cancer Immunology (Children’s Hospital of Philadelphia)

NEW Postdoctoral Position – Immunology (Benaroya Research Institute at Virginia Mason)

NEW Postdoctoral Position – Immunology and Cell Biology (Beth Israel Deaconess Medical Center)

Postdoctoral Positions – Immunology (Pasteur Institute)

Staff Scientist – Immunology (Benaroya Research Institute at Virginia Mason)

Postdoctoral Research Fellow – Molecular Oncology (Genentech, Inc.)

Professor – Immunology (La Jolla Institute for Allergy & Immunology)

Principal Investigator – The Role of Inflammation and the Immune Response in Regenerative Medicine (KU Leuven)

Postdoctoral Research Associate – Systems Immunology/Bioinformatics (Benaroya Research Institute at Virginia Mason (BRI))

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