Immune Regulation News Volume 9.02 | Jan 20 2017

TOP STORY

Systemic Immunity Is Required for Effective Cancer Immunotherapy

Cancer immunotherapies have focused heavily on local immune responses in the tumor microenvironment. The authors investigated immune activity more broadly, they performed an organism-wide study in genetically engineered cancer models using mass cytometry. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses

Scientists examined whether follicular dendritic cells (FDCs) retain self-antigens and the impact of this process in autoantibody secretion in lupus. They found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement. [Immunity] Abstract | Graphical Abstract

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb

Investigators demonstrated that mice lacking the transcription factor Myb in foxP3-expressing regulatory T (Treg) cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. [Immunity] Abstract | Graphical Abstract

Direct Control of Regulatory T Cells by Keratinocytes

Researchers found that the chromatin remodeler Mi-2β controls epidermal homeostasis by regulating the genes involved in keratinocyte and immune-cell activation to maintain an inactive state. Mi-2β depletion resulted in rapid deployment of both a pro-inflammatory and an immunosuppressive response in the skin. A key target of Mi-2β in keratinocytes is the pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP). Loss of TSLP receptor signaling specifically in regulatory T cells prevented their activation and permitted rapid progression from a skin pro-inflammatory response to a lethal systemic condition. [Nat Immunol] Abstract

Targeting Aurora Kinase a and JAK2 Prevents GVHD While Maintaining T_reg and Antitumor CTL Function

Scientists provide evidence that blocking Aurora A and Janus kinase 2 (JAK2) in human T cells is synergistic in vitro, prevents xenogeneic graft-versus-host disease (GVHD), and maintains antitumor responses by cytotoxic T lymphocytes (CTLs). Aurora A/JAK2 inhibition is immunosuppressive but permits the differentiation of inducible regulatory T cells that are hyperfunctional and CD39 bright and efficiently scavenge adenosine triphosphate. [Sci Transl Med] Abstract | Press Release

Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune Responses

Using synthetic pathogen-like particles (PLPs) that mimic physical properties of bacteria or large viruses, investigators discovered that the quality and quantity of Toll-like receptor 9 (TLR9) signaling by CpG in mouse dendritic cells are uniquely dependent on biophysical attributes; specifically, the surface density of CpG and size of the presenting PLP. [Cell Rep] Full Article | Press Release | Graphical Abstract

Targeting TNFR2 with Antagonistic Antibodies Inhibits Proliferation of Ovarian Cancer Cells and Tumor-Associated T_regs

Researchers characterized the effect of tumor necrosis factor receptor 2 (TNFR2) inhibition using antagonistic antibodies. In culture-based assays, they found that two TNFR2 antagonists inhibited T_reg proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion. [Sci Signal] Abstract | Press release

C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells

The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBPα, β, δ, and ε) were compared in v-Abl-immortalized primary B cells. Scientists showed conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBPα and β activation. High transgene expression of C/EBPβ or C/EBPε, but not of C/EBPα or C/EBPδ, also induced the formation of granulocytes. [Stem Cell Reports] Full Article | Graphical Abstract

Tsc1 Expression by Dendritic Cells Is Required to Preserve T-Cell Homeostasis and Response

Researchers showed that selective disruption of tuberous sclerosis complex 1 (Tsc1) in dendritic cells (DCs) results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mammalian target of rapamycin (mTOR)C1-PPARγ pathway, which leads to the upregulation of neuropilin-1 expression on DCs to stimulate naive T-cell proliferation. [Cell Death Dis] Full Article

Imbalance of Th17/Treg Cells in Pathogenesis of Patients with Human Leukocyte Antigen B27 Associated Acute anterior Uveitis

The authors investigated the role of Th17 and regulatory T cells’ imbalance in human leukocyte antigen B27-associated acute anterior uveitis. The percentages of Th17 and Treg cells, their molecular markers and related factors in peripheral blood of patients and healthy controls were measured by flow cytometry, real-time RT-PCR and ELISA. They observed a remarkable increase of CD4⁺ and CD4⁺IL^–17⁺ T cells in peripheral blood of patients compared to controls. [Sci Rep] Full Article

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Targeting TNFR2, an Immune Checkpoint Stimulator and Oncoprotein, Is a Promising Treatment for Cancer

Tumor necrosis factor receptor 2 (TNFR2) is expressed both by some cancer cells and by tumor-infiltrating immunosuppressive CD4⁺FoxP3⁺ regulatory T cells (T_regs). The authors discuss how TNFR2 stimulates the activation and proliferation of T_regs, a major checkpoint of antitumor immune responses, and promotes cancer cell survival and tumor growth. [Sci Signal] Abstract

TGF-β Regulation of Encephalitogenic and Regulatory T Cells in Multiple Sclerosis

The authors provide an analysis of the literature on the role that transforming growth factor-beta (TGF-β) plays in the generation and regulation of encephalitogenic and regulatory T cells in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), as well as in T cells of MS patients. [Eur J Immunol] Abstract

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Infinity Presents Preclinical Data and Phase I Clinical Data on IPI-549

Infinity Pharmaceuticals, Inc. presented preclinical data for IPI-549, an oral immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase-gamma. [Press release from Infinity Pharmaceuticals, Inc. discussing research presented at the Keystone Symposia Conference, “PI3K Pathways in Immunology, Growth Disorders and Cancer”, Santa Fe] Press Release

MD Anderson and EMD Serono Enter Three-Year Strategic Collaboration to Accelerate Development of Investigational Oncology/Immuno-Oncology Compounds

The University of Texas MD Anderson Cancer Center and EMD Serono announced a three-year strategic collaboration, with the aim of more quickly advancing the development of investigational cancer therapies in four cancers – breast, colorectal, glioblastoma and leukemia. [The University of Texas MD Anderson Cancer Center] Press Release

Lilly and Merck Expand Immuno-Oncology Collaboration

Eli Lilly and Company announced the expansion of an existing immuno-oncology collaboration with Merck through a subsidiary, to add a new study of Lilly’s LARTRUVO™ with KEYTRUDA® in patients with previously treated advanced or metastatic soft tissue sarcoma. [Eli Lilly and Company] Press Release

NIH Director Francis Collins Staying on — For Now

President-elect Donald Trump has decided to retain Francis Collins as director of the US National Institutes of Health (NIH) — at least temporarily. It is not clear whether Trump will formally reappoint Collins, or whether Collins will stay in his job only until Trump appoints a permanent director. [Nature News] Editorial

Gene-Edited Animals Face US Regulatory Crackdown

Researchers transforming animals with the latest genome-engineering tools may be disappointed by draft rules released by the US Food and Drug Administration (FDA). The most controversial of three proposed regulations declares that all animals whose genomes have been intentionally altered will be examined for safety and efficacy in a process similar to that for new drugs. Many researchers had hoped that the FDA would be less stringent about evaluating organisms whose genomes have been edited with precise tools — such as CRISPR and a separate technique called TALENs — than it is for animals that have been given DNA from different species or created using less-sophisticated means. [Nature News] Editorial

Billion-Dollar Project Aims to Prep Vaccines before Epidemics Hit

SARS, Zika, Ebola – when some of the world’s most terrifying disease outbreaks occur, health workers often find themselves powerless. A billion-dollar initiative aims to change that situation by pre-emptively developing and stockpiling vaccines to combat potential epidemic threats. [Nature News] Editorial

NEW IMMUNOLOGY 2017^TM
May 12-16, 2017
Washington, DC, United States

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NEW Postdoctoral Fellow – Dendritic Cell function in Gut Mucosa (Technical University of Denmark)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (Institute of Molecular and Cell Biology)

PhD Position – Cell Signaling, Gene Regulation and Quantitative Biology (Hebrew University of Jerusalem)

Scientist Positions – Immunology (New York Blood Center)

Senior Scientist (Immatics Biotechnologies GmbH)

Postdoctoral Position – Vascular Control of Immune Cell Infiltration and Metastasis (German Cancer Research Center)

Senior Scientist – Immunology (Immusoft Corporation)

Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

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