Volume 8.14 | Apr 22

Immune Regulation News 8.14 April 22, 2016
Immune Regulation News
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Researchers Show “Dirty Mice” Could Clean Up Immune System Research
Scientists developed a new way to study mice that better mimics the immune system of adult humans and which could significantly improve ways to test potential therapeutics. They describe the limitations of laboratory mice for immunology research and reveal the benefits of what they are calling “dirty mice.” [Press release from the University of Minnesota discussing online publication in Nature] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Noncanonical Autophagy Inhibits the Autoinflammatory, Lupus-Like Response to Dying Cells
Mice lacking any of several components of the LC3-associated phagocytosis (LAP) pathway show increased serum levels of inflammatory cytokines and autoantibodies, glomerular immune complex deposition, and evidence of kidney damage. When dying cells are injected into LAP-deficient mice, they are engulfed but not efficiently degraded and trigger acute elevation of pro-inflammatory cytokines but not anti-inflammatory interleukin-10. [Nature] Abstract | Press Release

Expansion and Activation of CD103+ Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition
Using mouse melanoma models, researchers found that CD103+ dendritic cells were the only antigen-presenting cells transporting intact antigens to the lymph nodes and priming tumor-specific CD8+ T cells. [Immunity] Abstract | Graphical Abstract

Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells
Using the K/BxN autoimmune arthritis model, scientists demonstrated that Peyer’s patch (PP) T follicular helper cells were essential for gut commensal segmented filamentous bacteria-induced systemic arthritis despite the production of auto-antibodies predominantly occurring in systemic lymphoid tissues, not PPs. [Immunity] Abstract | Graphical Abstract

Innate-Like Functions of Natural Killer T Cell Subsets Result from Highly Divergent Gene Programs
The authors analyzed purified populations of thymic natural killer T (NKT) cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. The data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. [Nat Immunol] Abstract

Silencing Spinal Interneurons Inhibits Immune Suppressive Autonomic Reflexes Caused by Spinal Cord Injury
Scientists showed that profound plasticity develops within spinal autonomic circuitry below an injury, creating a sympathetic anti-inflammatory reflex, and that chemogenetic silencing of this reflex circuitry blocks post-spianl cord injury immune suppression. [Nat Neurosci] Abstract | Press Release

Osteopontin Ablation Ameliorates Muscular Dystrophy by Shifting Macrophages to a Pro-Regenerative Phenotype
Investigators demonstrated that the improved dystrophic phenotype observed with osteopontin (OPN) ablation does not result from reductions in natural killer T cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. [J Cell Biol]
Abstract | Press Release

Biodegradable Antigen-Associated PLG Nanoparticles Tolerize Th2-Mediated Allergic Airway Inflammation Pre- and Postsensitization
Researchers hypothesized that antigen-associated nanoparticles, which they have used to prevent and treat T helper 1 (Th1)/Th17-mediated autoimmune disease, would also be effective for the induction of tolerance in a murine model of Th2-mediated ovalbumin/alum-induced allergic airway inflammation. [Proc Natl Acad Sci USA] Abstract | Press Release

Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice
Researchers determined the role of monocyte-derived macrophages in long-term spontaneous functional recovery after middle cerebral artery occlusion in mice. Analyses by flow cytometry and immunocytochemistry revealed that monocytes home to the stroke-injured hemisphere, and that infiltration peaks three days after stroke. [J Neurosci] Abstract | Press Release

A Novel Differentiation Pathway from CD4+ T Cells to CD4 T Cells for Maintaining Immune System Homeostasis
Investigators provide evidence that a novel differentiation pathway of CD4+ T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. [Cell Death Dis] Full Article

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Regulation of Immune Cell Function by Short-Chain Fatty Acids
The authors present a clear and updated description of the effects of short-chain fatty acids derived from bacteria on host immune system, as well as the molecular mechanisms involved. [Clin Transl Immunol] Full Article

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Immunotherapy Drug Shrinks Tumors in Half of Patients with Rare, Virus-Linked Skin Cancer
In a clinical trial of the immunotherapy drug pembrolizumab, half of 25 patients with a rare type of virus-linked skin cancer called Merkel cell carcinoma experienced substantial tumor shrinkage lasting nearly three times as long, on average, than with conventional chemotherapy. [Press release from The Johns Hopkins University discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Immune Design Presents New Preclinical Data on Advances of Two Separate Intratumoral Approaches
Immune Design announced the presentation of new preclinical data demonstrating broad anti-tumor activity of its ZVex™ platform and further evidence of the anti-tumor activity of G100, both via intratumoral administration. [Press release from Immune Design discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Targeting Cancer with Engineered T Cells
Dr. Philip Greenberg will describe how he and colleagues are genetically engineering T cells to seek out cancer cells, penetrate their defenses and kill them. [Press release from Fred Hutchinson Cancer Research Center (EurekAlert!) discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Study Supports Evidence that Rab Disruption May Be Effective Strategy for Treating Multiple Myeloma
Roswell Park Cancer Institute researchers are investigating agents that target and disrupt the trafficking of monoclonal antibodies in multiple myeloma, a cancer of the bone marrow. [Press release from Roswell Park Cancer Institute discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Affimed Presents Data on AFM13-Mediated Innate/Adaptive Immune Crosstalk
Affimed N.V. announced the presentation of preclinical data from a combination study of Affimed’s lead candidate AFM13 and checkpoint modulators. [Press release from Affimed N.V. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

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AbbVie, University of Chicago Collaborate to Advance Cancer Research
The University of Chicago and AbbVie have entered into a five-year collaboration agreement designed to improve the pace of discovery and advance medical research in oncology at both organizations. [The University of Chicago] Press Release

UChicago, Evelo Biosciences Sign Licensing Deal for Microbiome-Based Cancer Therapy
Evelo Biosciences and the University of Chicago have entered into an exclusive worldwide license agreement to develop and commercialize a microbiome-based cancer immunotherapy. The cancer therapy employs select gut microbes to boost the immune system’s attack on cancer cells and improve the efficacy of anti-cancer drugs. [The University of Chicago] Press Release

AbbVie and argenx to Collaborate on ARGX-115 against Novel Immuno-Oncology Target
AbbVie and argenx will collaborate to develop and commercialize ARGX-115. ARGX-115 is argenx’s preclinical-stage human antibody program targeting the novel immuno-oncology target GARP, a protein believed to contribute to immuno-suppressive effects of T-cells. [AbbVie Inc.] Press Release

Compugen Achieves Preclinical Milestone in Cancer Immunotherapy Collaboration with Bayer
Compugen Ltd. announced that it has achieved a first preclinical milestone for CGEN-15022 pursuant to its cancer immunotherapy collaboration with Bayer. The collaboration provides for the research, development, and commercialization of antibody-based cancer therapeutics against two novel Compugen-discovered immune checkpoint regulators, CGEN-15001T and CGEN-15022. [Compugen Ltd.] Press Release
US Agency Suspends Clinical Trials after Contamination Risk Discovered
The National Institutes of Health has suspended two of its manufacturing facilities that were found to be at risk of contaminating materials intended for use in patients. Oncologist Steven Rosenberg’s lab at the National Cancer Institute (NCI) is one of the two facilities affected. Rosenberg is developing cancer therapies using immune cells called T lymphocytes. After discovering problems with Rosenberg’s cell-manufacturing lab, the NCI suspended 13 trials that used materials from the facility. [Nature News] Editorial

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Postdoctoral Researchers – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

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