Volume 6.37 | Oct 3

Immune Regulation News 6.37 October 3, 2014
Immune Regulation News
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Loss of Signaling via Gα13 in Germinal Center B-Cell-Derived Lymphoma
Using in vitro and in vivo assays, scientists show that germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL)-associated mutations occurring in sphingosine-1-phosphate receptor-2 (S1PR2) frequently disrupt the receptor’s Akt and migration inhibitory functions. Gα13-deficient mouse germinal center B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. [Nature] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
mTOR- and HIF-1α-Mediated Aerobic Glycolysis as Metabolic Basis for Trained Immunity
Researchers studied a model of trained immunity, induced by the β-glucan component of Candida albicans, that was previously shown to induce nonspecific protection against both infections and malignancies. Genome-wide transcriptome and histone modification profiles were performed and pathway analysis was applied to identify the cellular processes induced during monocyte training. [Science] Abstract | Press Release

Continuous Requirement for the TCR in Regulatory T Cell Function
Scientists demonstrated that inducible ablation of the T cell antigen receptor (TCR) resulted in Treg cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2. [Nat Immunol] Abstract

The Same Self-Peptide Selects Conventional and Regulatory ​CD4+ T Cells with Identical Antigen Receptors
Researchers show that the binding of identical T-cell receptors (TCRs) to the same ubiquitously expressed MHC/peptide complex often directs thymocytes to both ​CD4+ lineages, indicating that the TCR affinity does not play the instructive role, and that restricted presentation of peptides in ‘thymic niches’ is not necessary for selection of ​CD4+​Foxp3+ T cells. [Nat Commun] Abstract

Tsc1 Promotes the Differentiation of Memory CD8+ T Cells via Orchestrating the Transcriptional and Metabolic Programs
Scientists describe that tuberous sclerosis 1 (Tsc1), a regulator of mechanistic target of rapamycin signaling, plays a crucial role in promoting the differentiation and function of memory CD8+ T cells in response to Listeria monocytogenes infection. [Proc Natl Acad Sci USA] Abstract

Association of the EF-Hand and PH Domains of the Guanine Nucleotide Exchange Factor SLAT with IP3 Receptor 1 Promotes Ca2+ Signaling in T Cells
Disruption of the SWAP-70-like adaptor of T cells (SLAT)-inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) interaction with cell-permeable, IP3R1-based fusion peptides inhibited T cell receptor-stimulated Ca2+ signaling, activation of the transcription factor NFAT, and production of cytokines, suggesting that this interaction is required for optimal T cell activation. [Sci Signal] Abstract

Blockade of mTOR Signaling via Rapamycin Combined with Immunotherapy Augments Anti-Glioma Cytotoxic and Memory T Cells’ Functions
Researchers demonstrate that administration of Rapamycin with Fms-like tyrosine kinase 3 ligand + thymidine kinase/ganciclovir immunotherapy enhanced the cytotoxic activity of anti-tumor CD8+ T cells. [Mol Cancer Ther] Abstract | Press Release

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity
Researchers used spinning disk confocal microscopy in Foxp3-GFP mice to visualize rolling of endogenous regulatory T cells (Tregs) in dermal postcapillary venules. Tregs underwent consistent but low-frequency rolling interactions under resting and inflamed conditions. [J Immunol] Abstract

Intramuscular Delivery of Heterodimeric IL-15 DNA in Macaques Produces Systemic Levels of Bioactive Cytokine Inducing Proliferation of NK and T Cells
Administration of DNAs expressing heterodimeric interleukin-15 (IL-15) resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8+NK cells, all memory CD8+ T-cell subsets and effector memory CD4+ T cells. [Gene Ther] Full Article

Lung Angiogenesis Requires CD4+Foxp3+ Regulatory T Cells
In a model of left lung ischemia, an increase in CD4+CD25+Foxp3+ cells was observed three to five days after the onset of ischemia in wild type C57Bl/6 mice. Using transgenic mice where Foxp3+ regulatory T cells (Treg) can be depleted with diphtheria toxin, scientists unexpectedly found that Foxp3+ Treg depletion led to markedly reduced lung angiogenesis. [Am J Respir Cell Mol Biol] Abstract

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T Cell Immune Abnormalities in Immune Thrombocytopenia
Studies regarding the roles of the new inducible costimulator signal transduction pathway, the ubiquitin proteasome pathway, and the nuclear factor kappa B signal transduction pathway in the induction of T cell tolerance can help improve our understanding of immune theory and may provide a new theoretical basis for studying the pathogenesis and treatment of immune thrombocytopenia. [J Hematol Oncol]
Abstract | Full Article

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Compugen Announces Presentations of Results for CGEN-15001 Supporting Immune Tolerance Induction
Compugen Ltd. announced that experimental results supporting CGEN-15001’s induction of long-term autoimmune disease remission in disease animal models, potentially through a novel mechanism of action, were presented. [Press release from Compugen Ltd. discussing research presented at the 3rd International Conference on Immune Tolerance, Amsterdam] Press Release

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Pfizer and Kyowa Hakko Kirin to Collaborate on Immuno-Oncology Combination Study
Pfizer Inc. and Kyowa Hakko Kirin announced that they have entered into an agreement to explore the therapeutic potential of the combination of Pfizer’s PF-05082566, an investigational, fully humanized monoclonal antibody that stimulates signaling through 4-1BB proliferation and survival, with Kyowa Hakko Kirin’s anti-CCR4 antibody mogamulizumab in a Phase Ib clinical study evaluating the safety and tolerability of the combination in patients with solid tumors. [Pfizer Inc.] Press Release

Foundation Responds to Eli Lilly and Company’s Release of Data from Clinical Trial of Tabalumab
The Lupus Foundation of America issued a statement in response to Eli Lilly and Company’s announcement of the results of two Phase III clinical trials of tabalumab, a biologic agent studied for the treatment of lupus. The trials did not show favorable results and the company is terminating these studies. [Lupus Foundation of America, Inc.] Press Release

Horwitz Prize Awarded for Work on Therapy that Uses the Immune System to Destroy Cancer Cells
Columbia University will award the 2014 Louisa Gross Horwitz Prize to James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center, for his work on understanding the process of T-cell activation and for developing therapies that harness the immune system to fight cancer. [Columbia University] Press Release
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NEW Digital Pathology Congress 2014
December 4-5, 2014
London, United Kingdom

NEW The Microbiome Forum: Asia 2015
January 19-20, 2015
Kuala Lumpur, Malaysia

NEW Biologics Congress 2015
February 2-3, 2015
Berlin, Germany

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NEW PhD Position – Immunoregulation (Jena University Hospital)

Postdoctoral Position – Immunometabolism (INSERM)

PhD Student – Calcium and Redox Signaling in Immune and Skin Cells (University of Saarland)

Postdoctoral Fellowship – Development of Autoimmunity and Cancer (Mount Sinai Medical Center)

Postdoctoral Researcher – Immune Response to Cancer (INSERM)

Postdoctoral Position – Immunology (Western New England University)

Faculty Positions – Cancer Immunotherapy and Tumor Microenvironment (NYU Langone Medical Center)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064)

PhD Studentship – Cancer Immunology (Cardiff University)

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.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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