Volume 7.35 | Sep 18

Immune Regulation News 7.35 September 18, 2015
Immune Regulation News
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Neutrophil Aging Is Regulated by the Microbiome
Using in vivo aging analyses in mice, researchers showed that neutrophil pro-inflammatory activity correlates positively with their aging whilst in circulation. Aged neutrophils represent an overly active subset exhibiting enhanced αMβ2 integrin activation and neutrophil extracellular trap formation under inflammatory conditions. [Nature] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity
Investigators showed that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired inteleukin-18 (IL-18) signaling. The inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of the death ligand FasL, and capacity to kill FasL-sensitive tumors. [Immunity] Abstract | Graphical Abstract | Press Release

Perforin-Positive Dendritic Cells Exhibit an Immuno-Regulatory Role in Metabolic Syndrome and Autoimmunity
Using bone marrow transplantation to generate animals selectively lacking dendritic cells rich in perforin-containing granules, researchers found that these chimeras progressively gained weight and exhibited features of metabolic syndrome. This phenotype was associated with an altered repertoire of T cells residing in adipose tissue and could be completely prevented by T cell depletion in vivo. [Immunity]
Full Article | Graphical Abstract | Press Release

Inhibition of Hyaluronan Synthesis Restores Immune Tolerance during Autoimmune Insulitis
Scientists demonstrated that hyaluronan (HA) is critical for the pathogenesis of autoimmune diabetes. An inhibitor of HA synthesis, 4-methylumbelliferone, reduced HA accumulation, constrained effector T cells to nondestructive insulitis, and increased numbers of intraislet FOXP3+ Tregs. [J Clin Invest]
Full Article | Press Release

GITR Subverts Foxp3+ Tregs to Boost Th9 Immunity through Regulation of Histone Acetylation
Researchers demonstrated that glucocorticoid-induced TNFR-related protein (GITR) ligation subverts the induction of Foxp3+ regulatory T cells (Tregs) and directs the activated CD4+ T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumor immunity in vivo. [Nat Commun]
Full Article | Press Release

Regulation of NKT Cell-Mediated Immune Responses to Tumors and Liver Inflammation by Mitochondrial PGAM5-Drp1 Signaling
Researchers demonstrated that receptor-interacting protein kinase 3 (RIPK3) plays an essential role in natural killer T (NKT) cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of NFAT and dephosphorylation of dynamin-related protein 1. [Nat Commun]
Full Article | Press Release

The B-Cell Antigen Receptor Integrates Adaptive and Innate Immune Signals
Scientists showed that the proliferative response of B cells to the latter stimuli is controlled by B-cell antigen receptor-dependent activation of phosphoinositidyl 3-kinase signaling. [Proc Natl Acad Sci USA]
Abstract | Full Article

Signal Strength Regulates Antigen-Mediated T-Cell Deceleration by Distinct Mechanisms to Promote Local Exploration or Arrest
The authors report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca2+ signals and actin-related protein 2/3 complex activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. [Proc Natl Acad Sci USA] Abstract | Full Article

Copy Number Variations of HLA-I and Activation of NKp30 Pathway Determine the Sensitivity of Gastric Cancer Cells to the Cytotoxicity of Natural Killer Cells
Researchers found that the tumorigenic capacity of human gastric cancer (GC) cell lines was dependent on the recruitment and activation of natural killer (NK) cells in xenograft tumors. They used whole-genome sequence on GC cell lines to identify potential genes controlling susceptibility to NK-mediated killing. [Oncogene] Abstract

CD4 T Cells Are Required for Both Development and Maintenance of Disease in a New Mouse Model of Reversible Colitis
Scientists developed a new model of reversible colitis in which adoptive transfer of CD4+CD45RBhi T cells into Helicobacter typhlonius–colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. [Mucosal Immunol] Abstract

CD8+NKT-Like Cells Regulate the Immune Response by Killing Antigen-Bearing DCs
The authors report that CD1d-independent CD8+NKT-like cells, which express both T cell markers and NK cell receptors, are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells (DCs). [Sci Rep] Full Article

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Autophagy and Autophagy-Related Proteins in the Immune System
The authors introduce advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity. [Nat Immunol] Abstract

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Cellular Biomedicine Group to Present CAR-T Phase I Clinical Trial Data for Non Small Cell Lung Cancer and Other Solid Tumors
Cellular Biomedicine Group Inc. announced that it would give an oral presentation to discuss Phase I clinical trial data for EGFR (HER-1)-targeted chimeric antigen receptor-modified T-cells (CAR-T) immunotherapy for patients with non-small cell lung cancer and other solid tumors. [Press release from Cellular Biomedicine Group Inc. discussing research to be presented at the 5th World Congress on Cancer Therapy, Atlanta] Press Release

TxCell to Present Its Cellular Immunotherapy Developments at Leading Cell and Ophthalmology Conferences
TxCell SA announced that Dr. Miguel Forte, chief operating officer, and Dr. Arnaud Foussat, chief scientific officer of TxCell, will present at three forthcoming leading cell and gene therapy and ophthalmology conferences. [Press release from TxCell SA discussing research to be presented at the International Society of Cellular Therapy (ISCT) Europe 2015 Regional Meeting, Seville; Phacilitate Cell & Gene Therapy Europe, Barcelona; and the European Association for Vision and Eye Research (EVER) 2015 Congress, Nice] Press Release

Idera Pharmaceuticals Presents New Intratumoral IMO-2125 Preclinical Data
Idera Pharmaceuticals, Inc. announced new preclinical data that showed cancer immunotherapy with intratumoral injections of IMO-2125 alone and in combination with ipilimumab demonstrated potent and systemic anti-tumor activity in preclinical cancer models. [Press release from Idera Pharmaceuticals, Inc. discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release | Poster 1 | Poster 2

Biothera’s Cancer Immunotherapy Drug Imprime PGG Elicits Increased Natural Killer Cell Activation and Cancer Cell Killing
Imprime PGG, Biothera’s late-stage investigational cancer immunotherapy drug, enhances the tumor killing function of the innate immune system’s natural killer cells. [Press release from Biothera discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

OncoMed Presents Immuno-Oncology Data for GITRL-Fc Candidate
OncoMed Pharmaceuticals, Inc. presented preclinical data for the company’s proprietary, wholly owned GITRL-Fc agent. [Press release from OncoMed Pharmaceuticals, Inc. discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

Heat Biologics to Present New Data on Its ComPACT Platform
Heat Biologics, Inc. announced that it will present a poster titled “Locally Secreted Fc-OX40L is Superior to Systemic, Antibody Mediated, OX40 Co-Stimulation for Combination Immunotherapy.” [Press release from Heat Biologics, Inc. discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

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Amgen and Xencor Announce Strategic Collaboration in Cancer Immunotherapy and Inflammation
Amgen and Xencor, Inc. announced that the two companies have entered into a research and license agreement to develop and commercialize novel therapeutics in the areas of cancer immunotherapy and inflammation. [Amgen Inc.] Press Release

HMS Receives $20 Million from Warren Alpert Foundation
The Warren Alpert Foundation has pledged $20 million to Harvard Medical School (HMS), a gift that embodies the school’s priorities of service, discovery and leadership. The foundation has earmarked $7.5 million to establish The Warren Alpert Foundation Discovery Fund for Immunologic Research. [Harvard Medical School] Press Release

TxCell Granted US Orphan Drug Designation for Col-Treg in the Treatment of Chronic Non-Infectious Uveitis
TxCell SA announced that the U.S. Food and Drug Administration’s Office of Orphan Products Development has granted Orphan Drug Designation to TxCell’s Col-Treg, a personalized T cell immunotherapy using collagen-II specific regulatory T-cells, for the treatment of chronic non-infectious uveitis. [TxCell SA] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 29th Annual Canadian Society for Immunology (CSI) Conference
April 1-4, 2016
Ottawa, Canada

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NEW Postdoctoral Position – Immunology (Sanofi)

NEW Professorship – Cellular and/or Molecular Biology and Immunology (The Rheumatology and Immunology Institute at the Nanjing University)

Postdoctoral Scientist – Immunology (University Hospital Heidelberg)

Postdoctoral Position – Immunology (Shanghai Institute of Immunology)

Postdoctoral Position – Immunology/Vascular Biology/Cancerology (University of Toulouse)

Postdoctoral Position – Neuroimmunology (Brain and Spine Institute (ICM))

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

Postdoctoral Fellow – Immunology (The Henry M. Jackson Foundation)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate – CRISPR-Based Therapeutics (Editas Medicine)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

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