Immune Regulation News Volume 8.11 | Apr 1 2016

Low-Voltage-Activated Ca_V3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles
Mice deficient for Ca_V3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor by central nervous system-infiltrating T helper 1 (Th1) and Th17 cells. [Immunity] Abstract

Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody
The authors report an innovative self-degradable microneedle (MN) patch for the sustained delivery of anti-PD-1 (aPD1) in a physiologically controllable manner. They found that a single administration of the MN patch induced robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. [Nano Lett] Abstract | Press Release

IL-15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors
Scientists showed that most inhibitors targeting multiple signaling pathways have especially strong negative effects on T cell activation at their active doses on cancer cells. They found that recently approved MEK inhibitors displayed potent suppressive effects on T cells in vitro. [Cancer Res] Abstract | Press Release

Immunotherapy with a HER2 Targeted Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma
Investigators used dogs with HER2/neu⁺ appendicular osteosarcoma to determine whether a highly attenuated, recombinant Listeria monocytogenes expressing a chimeric human HER2/neu fusion protein could safely induce HER2/neu specific immunity and prevent metastatic disease. [Clin Cancer Res] Abstract | Press Release

Immunoproteasome Dysfunction Augments Alternative Polarization of Alveolar Macrophages
Investigators analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells. [Cell Death Differ] Abstract | Press Release

Critical Role of Caspase-8-Mediated IL-1 Signaling in Promoting Th2 Responses during Asthma Pathogenesis
Scientists used a mouse model of ovalbumin-induced asthma to identify a crucial role for caspase-8 in the development of allergic airway inflammation. Caspase-8 was required for the production of interleukin (IL)-1 cytokines to promote Th2 immune response, which promotes the development of pulmonary eosinophilia and inflammation. [Mucosal Immunol] Abstract

A Large Rab GTPase Encoded by CRACR2A Is a Component of Subsynaptic Vesicles that Transmit T Cell Activation Signals
Through experiments involving gene silencing in cells and knockout mice, scientists demonstrated a role for CRACR2A (Ca²⁺ release–activated Ca²⁺ channel regulator 2A) in the activation of the Ca²⁺ and c-Jun N-terminal kinase signaling pathways in response to T cell receptor stimulation. [Sci Signal] Abstract

Crucial Roles of XCR1-Expressing Dendritic Cells and the XCR1-XCL1 Chemokine Axis in Intestinal Immune Homeostasis
Researchers showed that mice lacking XCR1⁺ dendritic cells are specifically deficient in intraepithelial and lamina propria T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death, and are also more susceptible to chemically-induced colitis. [Sci Rep] Full Article

IL-12 and IL-4 Activate a CD39-Dependent Intrinsic Peripheral Tolerance Mechanism in CD8⁺ T Cells
Researchers showed CD8⁺ regulatory T cells also express high level CD39, an ecto-nucleotidase that degrades extracellular ATP, and this contributes to their suppressive activity. CD39 expression was found to be upregulated on CD8⁺ T cells during peripheral tolerance induction in vivo, accompanied by release of interleukin (IL)-12 and IL-10. [Eur J Immunol] Abstract

LV305, a Dendritic Cell-Targeting Integration-Deficient ZVex™-Based Lentiviral Vector Encoding NY-ESO-1, Induces Potent Anti-Tumor Immune Response
Scientists engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. [Mol Ther Oncolytics] Full Article

Expression of DAI by an Oncolytic Vaccinia Virus Boosts the Immunogenicity of the Virus and Enhances Antitumor Immunity
Investigators developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI) to boost the innate immune system and to activate adaptive immune cells in the tumor. Treatment with DAI-armed VV resulted in significant reduction in the size of syngeneic melanoma tumors in mice. [Mol Ther Oncolytics] Full Article

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Aduro Biotech Helps Launch New Immunotherapy, Vaccine Effort
UC Berkeley cancer immunologists are teaming up with colleagues working on infectious disease to create a new Immunotherapeutics and Vaccine Research Initiative, fueled by $7.5 million in funding from Aduro Biotech Inc. [University of California, Berkeley] Press Release | Video

CHOP Oncologist Receives $1 Million Hyundai Quantum Grant to Improve Leukemia Treatment
A physician-researcher at The Children’s Hospital of Philadelphia (CHOP) has received a $1 million Hyundai Quantum Grant from Hyundai Hope on Wheels to advance treatment for a high-risk form of childhood leukemia. The research focuses on immunotherapy—an approach that utilizes a patient’s immune system to better fight off cancer. [The Children’s Hospital of Philadelphia] Press Release

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