Volume 8.07 | Feb 26

Immune Regulation News 8.07 February 26, 2016
Immune Regulation News
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Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing
Scientists investigated whether synaptic forces promote the destruction of target cells. They found that increasing target cell tension augmented pore formation by perforin and killing by cytotoxic T lymphocytes. [Cell] Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Macrophage Akt1 Kinase-Mediated Mitophagy Modulates Apoptosis Resistance and Pulmonary Fibrosis
Investigators showed Akt1 induced macrophage mitochondrial reactive oxygen species and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages and Park2−/− mice had impaired mitophagy and reduced active transforming growth factor-β1. [Immunity] Abstract | Graphical Abstract | Press Release

Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells
Scientists report that, driven by commensal fungi, a wave of CD45+CD103+RALDH+ cells migrate to the peripheral lymph nodes after birth. The arrival of these cells introduced high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directed the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. [Immunity] Abstract | Graphical Abstract

The MicroRNA miR-148a Functions as a Critical Regulator of B Cell Tolerance and Autoimmunity
Researchers performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. [Nat Immunol] Abstract | Press Release

Stromal Cells Control the Epithelial Residence of DCs and Memory T Cells by Regulated Activation of TGF-β
Researchers found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes and maintained the epidermal residence of Langerhans cells and CD8+ tissue-resident memory T cells by activating latent transforming growth factor-β1 (TGF-β). [Nat Immunol] Abstract

The Adaptive Immune System Restrains Alzheimer’s Disease Pathogenesis by Modulating Microglial Function
To test the hypothesis that adaptive immunity influences Alzheimer’s disease (AD) pathogenesis, scientists generated an immune-deficient AD mouse model that lacks T, B, and natural killer cells. The resulting “Rag-5xfAD” mice exhibited a greater than twofold increase in β-amyloid (Aβ) pathology. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Lymphocyte-Activation Gene 3+ (LAG3+) Forkhead Box Protein 3 (FOXP3) Regulatory T Cells Induced by B Cells Alleviates Joint Inflammation in Collagen-Induced Arthritis
The authors developed optimal potential induced regulatory T cell (iTreg)-based therapy for collagen-induced arthritis by adoptively transferring LAG3+ Treg-of-B cells. B-cell-induced Treg-of-B cells expressed LAG3 but not Foxp3, and secreted IL-4, IL-10, and TGF-β. [J Autoimmun] Abstract

Cell Intrinsic Role of NF-κB-Inducing Kinase in Regulating T Cell-Mediated Immune and Autoimmune Responses
Using T cell-conditional NF-κB inducing kinase (NIK) knockout mice, investigators demonstrated that although NIK is dispensable for thymocyte development, it has a cell-intrinsic role in regulating the homeostasis and function of peripheral T cells. [Sci Rep] Full Article

TLR5 Mediates CD172α+ Intestinal Lamina Propria Dendritic Cell Induction of Th17 Cells
By using a microbiota antigen-specific T cell reporter mouse system, researchers demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal lamina propria, but not in the spleen when transferred into TCRβxδ−/− mice. [Sci Rep] Full Article

A Novel Multi-Drug Metronomic Chemotherapy Significantly Delays Tumor Growth in Mice
The counterbalance effect of a novel metronomic chemotherapy protocol on an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. [J Transl Med] Full Article

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Antitumor Actions of Interferons: Implications for Cancer Therapy
As interferons (IFNs) can be produced by, and act on, both tumor cells and immune cells, understanding this reciprocal interaction will enable the development of improved single-agent or combination therapies that exploit IFN pathways and new ‘omics’-based biomarkers to indicate responsive patients. [Nat Rev Cancer] Abstract

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Kadmon to Present Preclinical Data Demonstrating ROCK2 Signaling as a Key Regulator of T Follicular Helper Cell Function in Autoimmune Conditions
Kadmon Corporation, LLC announced preclinical data demonstrating that selective inhibition of rho-associated coiled-coil kinase 2 (ROCK2) significantly decreased the development and function of cells involved in the inflammatory response while preserving normal immune system function, supporting the potential of targeted ROCK2 inhibition to treat autoimmune disease. [Press release from Kadmon Corporation, LLC discussing research to be presented at the 2016 Keystone Symposia Conference – T Follicular Helper Cells and Germinal Centers, Monterey] Press Release

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Neon Therapeutics Enters Collaborative Research Agreement with the Netherlands Cancer Institute
Neon Therapeutics announced that the company has entered into a collaborative research agreement with the Netherlands Cancer Institute’s (NKI) Antoni van Leeuwenhoek Hospital and the Amsterdam Biotherapeutics Unit. Under the terms of the agreement, Neon Therapeutics and NKI will combine complementary capabilities to develop personalized T cell therapeutics. [Neon Therapeutics] Press Release

La Jolla Institute Receives $5 Million Gift from Pfizer
La Jolla Institute for Allergy and Immunology has received a $5 million gift, which will help establish the Mission Support for Cancer Immunology and Oncology Research. The Institute will use the majority of the funds to establish the Pfizer Endowed Chair in Cancer Immunology and Oncology and support research on the immune system and oncology. [La Jolla Institute for Allergy and Immunology] Press Release

CAR Trials Drive Leukemia and Lymphoma Treatment in New Direction
Researchers at UC San Diego Moores Cancer Center have launched three clinical trials to test the safety and efficacy of a novel cellular-immunotherapy that uses modified T cells – one of the immune system’s primary weapons – to treat three different types of blood cancer that often defy existing therapies. [UC San Diego Health] Press Release

Cancer Research UK Launches Trial for Potential New Drug that Could Help Immune System Fight Cancer
Cancer Research UK’s Centre for Drug Development, in partnership with Amgen Inc., has launched a new clinical trial to test a drug that could stop a patient’s immune system from protecting tumors. [Cancer Research UK] Press Release

Juno Therapeutics, Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center Announce New Immuno-Oncology Clinical Trials Unit
Juno Therapeutics, Inc. and Fred Hutchinson Cancer Research Center announced the creation of a new, best-in-class clinical trials unit dedicated to immuno-oncology. [Juno Therapeutics, Inc.] Press Release

TapImmune Receives Notice of Allowance on U.S. Patent Claims for PolyStart – Next-Generation T-Cell Vaccine
TapImmune, Inc. announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for its patent application entitled, “A chimeric nucleic acid molecule with non-AUG initiation sequences.” The patent claims are for the company’s proprietary PolyStart™ technology which is a platform for the next-generation vaccine technology for the treatment of cancer or infectious diseases. [TapImmune, Inc.] Press Release
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NEW World Stem Cells & Regenerative Medicine Congress
May 18-20, 2016
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NEW Postdoctoral Fellow – Clinical Immunology (Benaroya Research Institute at Virginia Mason)

NEW Postdoctoral Fellow – Antibody-Based Therapeutics (Inserm)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Autoimmune, Inflammatory and Demyelinating Diseases (Queen’s University Belfast)

Postdoctoral Positions – Innate Immunity and Autoimmunity (UT Southwestern Medical Center)

Faculty Positions – Immunology (University of Texas Health Science Center)

Senior Scientist – Immunology (Bavarian Nordic GmbH)

Assistant or Associate Professor – Immunity and Tolerance (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Position – Immunology (Indiana University)

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