Volume 6.18 | May 23

Immune Regulation News 6.18 May 23, 2014
Immune Regulation News
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Researchers Find New Molecule to Treat Asthma
Researchers identified a novel molecule that prevents T-cells from orchestrating asthma brought on by allergens. The findings show promise for a new potent therapeutic agent to treat asthma, a chronic disease affecting more than 25 million Americans. [Press release from Sanford Burnham Medical Research Institute discussing online prepublication in Proceedings of the National Academy of Sciences, USA] Press Release | Abstract
Learn more about the new smartphone app for human blood cell frequencies
PUBLICATIONS (Ranked by impact factor of the journal)
Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival
Suppressed immune surveillance with increased CD4+Foxp3+ T regulatory cells was observed in myofibroblast-depleted mouse tumors. Although myofibroblast-depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed disease acceleration and prolonged animal survival. [Cancer Cell] Abstract

miR-155 Activates Cytokine Gene Expression in Th17 Cells by Regulating the DNA-Binding Protein Jarid2 to Relieve Polycomb-Mediated Repression
Researchers found defective T helper 17 (Th17) cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and regulatory T cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 to chromatin. [Immunity]
Abstract | Graphical Abstract

Lymph Node Stromal Cells Acquire Peptide-MHCII Complexes from Dendritic Cells and Induce Antigen-Specific CD4+ T Cell Tolerance
Researchers found a novel, alternative mechanism where lymph node-resident stromal cells tolerize CD4+ T cells through the presentation of self-antigens via transferred peptide-MHCII complexes of dendritic cell origin. [J Exp Med] Abstract

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy
Tumor signaling of programmed death 1 (PD1) on T cells and expansion of myeloid-derived suppressor cells (MDSCs) are major mechanisms of tumor immune escape. Researchers sought to target these pathways in rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. [Sci Transl Med] Abstract

Adenosine Triphosphate Acts as a Paracrine Signaling Molecule to Reduce the Motility of T Cells
Investigators showed a novel form of cell-to-cell communication based on adenosine triphosphate (ATP). ATP released by stimulated T cells induces P2X4/P2X7-mediated calcium waves in neighboring lymphocytes. Data obtained in lymph node slices suggest that, during T-cell priming, ATP acts as a paracrine messenger to reduce the motility of lymphocytes and that this may be relevant to allow optimal tissue scanning by T cells. [EMBO J] Abstract

Foxp3+ Regulatory T Cells Promote Lung Epithelial Proliferation
Scientists demonstrated that intratracheal delivery of endotoxin (lipopolysaccharide) elicits alveolar epithelial damage from which the epithelium undergoes proliferation and repair. Epithelial proliferation coincided with an increase in Foxp3+ regulatory T cells in the lung during the course of resolution. [Mucosal Immunol] Abstract

IL-15 Induces Alloreactive CD28 Memory CD8 T Cell Proliferation and CTLA4-Ig Resistant Memory CD8 T Cell Activation
Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28 memory CD8 T cell proliferation. Addition of interleukin (IL)-15, but not IL-2 or IL-7, to co-cultures of CD28 or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28 and enhanced CD28+ memory T cell proliferation. [Am J Transplant] Abstract

Expression of IL-2 in β Cells by AAV8 Gene Transfer in Pre-Diabetic NOD Mice Prevents Diabetes through Activation of FoxP3-Positive Regulatory T Cells
The local β-cell expression of interleukin (IL)-2 increased the number of CD4+CD25+FoxP3+ cells in the pancreatic lymph node and SPL in both non-obese diabetic (NOD) and C57BL/6 mice. Results demonstrate that local, low expression of mIL-2 in islets prevents progress of diabetes through the regulation of regulatory T cells. [Gene Ther] Abstract

Murine Th9 Cells Promote the Survival of Myeloid Dendritic Cells in Cancer Immunotherapy
In melanoma B16-OVA tumor-bearing mice, dendritic cells (DCs) conditioned by T-helper (Th)-9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that interleukin (IL)-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. [Cancer Immunol Immunother] Abstract

Induction of Antigen-Specific Cytotoxic T Lymphocytes by Fusion Cells Generated from Allogeneic Plasmacytoid Dendritic and Tumor Cells
Two types of allogeneic cells, a leukemia plasmacytoid dendritic cell (pDC) line (PMDC05) and pancreatic cancer cell lines (PANC-1 or MIA PaCa-2), were fused instead of autologous monocyte-derived dendritic cells and tumor cells. Scientists created four types of pDC/tumor fusion cells by alternating fusion partners and treating with lipopolysaccharide and examined their antitumor immune responses. [Int J Oncol] Abstract

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Positive and Negative Selection of the T Cell Repertoire: What Thymocytes See (and Don’t See)
Authors discuss how the particular composition of the peptide-MHC ligandomes that are presented by specific antigen-presenting cells subsets not only shapes the T cell repertoire in the thymus but may also indelibly imprint the behavior of mature T cells in the periphery. [Nat Rev Immunol] Abstract

No Receptor Stands Alone: IgG B-Cell Receptor Intrinsic and Extrinsic Mechanisms Contribute to Antibody Memory
Investigators summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory. [Cell Res] Full Article

B Cells with Immune-Regulating Function in Transplantation
Authors review the current understanding of the various phenotypes and roles that have been associated with immune-regulating B cells. They also discuss the mechanisms employed by subsets of these regulatory B cells to control the immune response in transplant recipients and in animal models of transplantation. [Nat Rev Nephrol] Abstract

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SKC Partners with UK Charities to Launch International Neuroblastoma Clinical Trial
The grant amount of $400,000 will create a new immunotherapy treatment option in the US, UK, and in Spain, for children with relapsed or refractory disease. [Solving Kids’ Cancer] Press Release

Col-Treg Granted Advanced Therapy Medicinal Product Classification by the European Medicines Agency
TxCell SA announced that Col-Treg, its second therapeutic candidate from its ASTrIA platform, has been granted Advanced Therapy Medicinal Product classification by the Committee for Advanced Therapies of the European Medicines Agency. [TxCell SA] Press Release

FDA Approves Takeda’s Entyvio™ (vedolizumab) for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease
Takeda Pharmaceutical Company Limited and its wholly-owned subsidiary, Takeda Pharmaceuticals U.S.A., Inc., announced that the United States Food and Drug Administration (FDA) simultaneously approved a new biologic therapy, Entyvio™ (vedolizumab), for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease. [Takeda Pharmaceutical Company Limited] Press Release

Bristol-Myers Squibb and Celldex Therapeutics Announce Clinical Trial Collaboration to Evaluate the Combination of Investigational Immunotherapies Nivolumab and Varlilumab
Bristol-Myers Squibb Company and Celldex Therapeutics, Inc. announced that they have entered into a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of nivolumab, Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, and varlilumab, Celldex’s CD27 targeting investigational antibody in a Phase I/II study. [Bristol-Myers Squibb Company] Press Release

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Therapeutic Goods Administration (Australia)
NEW FASEB Science Research Conferences – Biology of the Immune System
June 29 – July 4, 2014
Snowmass Village, United States

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NEW Postdoctoral Position – Biology of Memory B Cells (Medical Research Council)

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

Postdoctoral Research Fellow – Allergic Lung Inflammation (Singapore Immunology Network)

Postdoctoral Position – Cell Death and Inflammation (Inflammation Research Center – VIB-UGent)

Postdoctoral Position – Cell and Extracellular Matrix Biology (Johns Hopkins University)

Principal Investigator – Molecular Mechanisms of Inflammation (Inflammation Research Center – VIB-UGent)

Postdoctoral Fellow – Microbiology and Immunology (McGill University)

Postdoctoral Research Associate – Functional Cross-Talk between T Lymphocytes and NK Cells (Meharry Medical College School of Medicine)

Postdoctoral Associate/Research Scientist – Macrophage Biology (Massachusetts Institute of Technology – MIT)

Postdoctoral Associate – Immunology (Virginia Bioinformatics Institute at Virginia Tech)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – hPSC (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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