Volume 2.42 | Nov 4

Human Immunology News 2.42 November 4, 2014
Human Immunology News
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Genetic and Epigenetic Fine Mapping of Causal Autoimmune Disease Variants
The authors developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. They integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4+ T-cell subsets, regulatory T cells, CD8+ T cells, B cells, and monocytes. [Nature]
Abstract | Press Release
View Data: UM729, a Novel Small Molecule for Ex Vivo Expansion of Human hSCs
PUBLICATIONS (Ranked by impact factor of the journal)
A Spaetzle-Like Role for Nerve Growth Factor β in Vertebrate Immunity to Staphylococcus aureus
Nerve growth factor β was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. [Science] Abstract

Molecular Profiling Reveals a Tumor-Promoting Phenotype of Monocytes and Macrophages in Human Cancer Progression
Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. Investigators used molecular profiling combined with functional assays to investigate the role of these cells in human renal cell carcinoma. [Immunity] Abstract

Human NLRP3 Inflammasome Senses Multiple Types of Bacterial RNAs
Investigators report that all three types of bacterially derived RNA (mRNA, tRNA, and rRNAs) were capable of activating the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome in human macrophages. [Proc Natl Acad Sci USA] Abstract

Cellular and Molecular Immune Profiles in Renal Transplant Recipients after Conversion from Tacrolimus to Sirolimus
Tacrolimus and sirolimus are commonly used maintenance immunosuppressants in kidney transplantation. As their effects on immune cells and allograft molecular profiles have not been elucidated, scientists characterized the effects of tacrolimus to sirolimus conversion on the frequency and function of T cells, and on graft molecular profiles. [Kidney Int] Abstract

Expression Profiles of Long Non-Coding RNAs Located in Autoimmune Disease-Associated Regions Reveal Immune Cell Type Specificity
Scientists characterized long non-coding RNA transcripts and protein-coding genes located in loci associated with nine autoimmune and immune-related disorders which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes and four populations of cord blood-derived T-helper cells. [Genome Med] Abstract | Full Article

Novel Expression of Neuropilin 1 on Human Tumor-Infiltrating Lymphocytes in Colorectal Cancer Liver Metastases
Scientists investigated neuropilin 1 (NRP1) expression on tumor-infiltrating lymphocytes and peripheral blood mononuclear cells (PBMCs) from colorectal cancer liver metastases. PBMCs were co-cultured in vitro with tumor tissue and analyzed for NRP1 expression. [Expert Opin Ther Targets] Abstract

Estrogen Upregulates MICA/B Expression in Human Non-Small Cell Lung Cancer through the Regulation of ADAM17
Whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. Investigators found that estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of natural killer (NK)92 cells and impaired the cytotoxic activity of NK cells. [Cell Mol Immunol] Abstract

The Presence of Interleukin-27 during Monocyte-Derived Dendritic Cell Differentiation Promotes Improved Antigen Processing and Stimulation of T Cells
Researchers show that interleukin (IL)-27 treatment during monocyte-derived dendritic cell (DC) differentiation enhanced the ability to process antigens and stimulate T cell activity. DCs differentiated in the presence of IL-27 showed enhanced acidification of latex bead-containing phagosomes that was consistent with elevated expression of vacuolar-ATPases. [Immunology] Abstract

Amniotic Membrane Mesenchymal Cells-Derived Factors Skew T Cell Polarization toward Treg and Downregulate Th1 and Th17 Cells Subsets
In order to understand the mechanisms involved in immune regulation exerted by human amniotic mesenchymal stromal cells (hAMSC), researchers analyzed the effects of conditioned medium derived from the culture of hAMSC on T-cell polarization towards Th1, Th2, Th17, and T-regulatory (Treg) subsets. [Stem Cell Rev Rep] Full Article

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Role of Interleukin-21 in HBV Infection: Friend or Foe?
The authors review the current knowledge on the critical role of interleukin (IL)-21 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-21 derived from virus-specific CD4+ T cells plays key roles in sustaining CD8+ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, IL-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. [Cell Mol Immunol] Abstract

Epstein-Barr Virus and Multiple Sclerosis: Potential Opportunities for Immunotherapy
Many observations implicate Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis, namely universal EBV seropositivity, high anti-EBV antibody levels, alterations in EBV-specific CD8+ T-cell immunity, increased spontaneous EBV-induced transformation of peripheral blood B cells, increased shedding of EBV from saliva and accumulation of EBV-infected B cells and plasma cells in the brain. [Clin Transl Immunol] Full Article

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UTHealth Research Shows Mushroom Extract, AHCC, Helpful in Treating HPV
A Japanese mushroom extract appears to be effective for the eradication of human papillomavirus (HPV), according to a pilot clinical trial at The University of Texas Health Science Center at Houston (UTHealth) Medical School. [Press release from The University of Texas Health Science Center at Houston discussing research presented at the 11th International Conference of the Society for Integrative Oncology (SIO), Houston] Press Release

Receptos Reports Positive Phase II Results for TOUCHSTONE Trial of RPC1063 in Ulcerative Colitis
Receptos, Inc. announced that TOUCHSTONE, the Phase II trial of RPC1063 in ulcerative colitis, met its primary endpoint and all secondary endpoints with statistical significance in the eight-week induction period. [Receptos, Inc.] Press Release

Phase II Objective Response Rate and Survival Data for Opdivo (Nivolumab) in Heavily Pre-treated Advanced Squamous Cell Non-Small Cell Lung Cancer
Bristol-Myers Squibb Company announced results from CheckMate-063, a Phase II single-arm, open-label study of Opdivo, an investigational PD-1 immune checkpoint inhibitor, administered as a single agent in patients with advanced squamous cell non-small cell lung cancer. [Bristol-Myers Squibb Company] Press Release

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NRC and AvidBiologics Progress New Treatments to Seek and Destroy Cancer Cells
AvidBiologics Inc. and the National Research Council of Canada (NRC) are collaborating on one of the most promising advances in the fight against cancer: antibody-drug conjugates (ADCs). Recently signed research and licensing agreements will enable both organizations to continue developing a series of ADCs targeting breast, lung, and head-and-neck cancers. [National Research Council of Canada] Press Release

Bristol-Myers Squibb Enters into Agreement that Provides an Exclusive Option to Acquire F-star Alpha Ltd. and Its Novel HER2-Targeted Therapy
Bristol-Myers Squibb Company and F-star Alpha Ltd. announced that the companies have entered into an agreement that provides Bristol-Myers Squibb the exclusive option to acquire F-star Alpha Ltd, and gain worldwide rights to its lead asset FS102. FS102 is a novel Phase I ready human epidermal growth factor receptor 2 (HER2)-targeted therapy in development for the treatment of breast and gastric cancer. [Bristol-Myers Squibb Company] Press Release

Xencor Renegotiates XmAb®5871 Agreement with Amgen; Regains All Rights and Plans Clinical Development in Rare Autoimmune Disease
Xencor, Inc. announced that it has regained all development and commercial rights to XmAb®5871 by seeking and obtaining a termination of the prior option and collaboration agreement and executing a new right-of-first-negotiation agreement with Amgen. XmAb5871 is a first-in-class monoclonal antibody containing Xencor’s proprietary immune inhibitor XmAb Fc domain that targets FcγRIIb to inhibit B-cell function. [Xencor, Inc.] Press Release

Profectus BioSciences Receives $9.5 Million Department of Defense Funding to Manufacture Trivalent VesiculoVax™-Vectored Vaccine to Protect against All Ebola and Marburg Viruses
Profectus BioSciences, Inc. announced that the Department of Defense has contracted the manufacture and IND-enabling preclinical testing of the Profectus trivalent Ebola/Marburg vaccine. [Profectus BioSciences, Inc.] Press Release

CEL-SCI Enrolls 22 Patients during October in Its Phase III Immunotherapy Head and Neck Cancer Trial
CEL-SCI Corporation announced that during the month of October the company enrolled 22 patients with advanced primary, not yet treated, head and neck cancer into its global pivotal Phase III head and neck cancer trial for its investigational immunotherapy Multikine (leukocyte interleukin, injection). [CEL-SCI Corporation] Press Release
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NEW ESH International Conference on New Concepts in B Cell Malignancies: From Molecular Pathogenesis to Personalized Treatment (ESH 2014)
November 14-16, 2014
Thessaloniki, Greece

NEW Cell & Gene Therapy Forum 2015
January 26-28, 2015
Washington DC, United States

NEW Keystone Symposia – Antibodies as Drugs: Immunological Scaffolds as Therapeutics
February 8-13, 2015
Banff, Canada

Visit our events page to see a complete list of events in the human immunology community.
NEW Research Associate – Interleukin-17 Producing T Cells in Rheumatic Disease (King’s College London)

NEW Postdoctoral Position – Tumor Immunology (Cancer Research Center of Lyon)

NEW PhD Studentship – Role of Mucus on the Impact of Gut Bacteria on Health (University of East Anglia)

NEW Postdoctoral Fellow – Immunology and/or Virology (University of Bergen)

NEW Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

Postdoctoral Position – Experimental Vascular Biology (Academic Medical Center)

PhD Studentship – Effects of Probiotics on Immunity in the Human Ageing Gut (University of East Anglia)

Postdoctoral Fellow – Interleukin 23 in the Pathogenesis of Systemic Lupus Erythematosus (Beth Israel Medical Center)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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