Immune Regulation News Volume 8.16 | May 6 2016

The EGFR-Specific Antibody Cetuximab Combined with Chemotherapy Triggers Immunogenic Cell Death
Scientists found that cetuximab, in combination with chemotherapy, fostered immunogenic cell death in colorectal cancer cells, which was measured via the endoplasmic reticulum stress response and an increase in phagocytosis by dendritic cells. [Nat Med] Abstract

Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction
Scientists developed a cerebrovascular rupture system in zebrafish by using multi-photon laser, which generates a lesion with two endothelial ends. In vivo time-lapse imaging showed that a macrophage arrived at the lesion and extended filopodia or lamellipodia to physically adhere to both endothelial ends. [Immunity] Abstract | Graphical Abstract | Press Release | Video

Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands
Scientists deleted Tgfbr2 in cells expressing the innate lymphoid cell (ILC) and NK marker NKp46 and found that salivary gland ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. [Immunity] Abstract | Graphical Abstract

A TRAF-Like Motif of the Inducible Costimulator ICOS Controls Development of Germinal Center T_FH Cells via the Kinase TBK1
Alteration of ICOS or depletion of TBK1 in T cells severely impaired the differentiation of germinal center (GC) follicular helper T cells (T_FH cells) and the development of GCs, interfered with B cell differentiation and disrupted the development of antibody responses, but the IProx motif and TBK1 were dispensable for the early differentiation of T_FH cells. [Nat Immunol] Abstract | Press Release

Expression Profiling of Constitutive Mast Cells Reveals a Unique Identity within the Immune System
Researchers assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. They found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. [Nat Immunol] Abstract

Alternatively Activated Macrophages Determine Repair of the Infarcted Adult Murine Heart
Scientists identified CD206⁺F4/80⁺CD11b⁺ alternatively activated-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after myocardial infarction. [J Clin Invest] Full Article | Press Release

DNA-Based Nanoparticle Tension Sensors Reveal that T-Cell Receptors Transmit Defined pN Forces to Their Antigens for Enhanced Fidelity
Researchers developed DNA-based gold nanoparticle tension sensors to provide the first pN tension maps of individual T-cell receptor (TCR)-peptide-major histocompatibility complex complexes during T-cell activation. They showed that naïve T cells harness cytoskeletal coupling to transmit 12–19 pN of force to their TCRs within seconds of ligand binding and preceding initial calcium signaling. [Proc Natl Acad Sci USA]
Abstract | Press Release | Video

Thy1⁺IL-7⁺ Lymphatic Endothelial Cells in iBALT Provide a Survival Niche for Memory T-Helper Cells in Allergic Airway Inflammation
Investigators found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic T helper cells capable of driving allergic inflammation are maintained within the iBALT structures. [Proc Natl Acad Sci USA] Abstract | Full Article

Transcription Factor KLF2 Regulates Homeostatic NK Cell Proliferation and Survival
In terms of natural killer (NK) cell expansion and survival, researchers report that Kruppel-like factor 2 (KLF2) is a key transcription factor that underpins both of these events. Excision of Klf2 using gene-targeted mouse models promotes spontaneous proliferation of immature NK cells in peripheral tissues, a phenotype that is replicated under ex vivo conditions. [Proc Natl Acad Sci USA] Abstract

Notch Signaling in Group 3 Innate Lymphoid Cells Modulates Their Plasticity
Scientists demonstrated that the population of natural cytotoxicity receptor–positive type 3 innate lymphoid cells in mice is composed of two subsets that have distinct developmental requirements. [Sci Signal] Abstract

Transforming Growth Factor–β and Notch Ligands Act as Opposing Environmental Cues in Regulating the Plasticity of Type 3 Innate Lymphoid Cells
Through genetic mapping, investigators identified a previously uncharacterized subset of natural cytotoxicity receptor (NCR)⁻ group 3 innate lymphoid cells (ILC3s) in mice that transiently express Ncr1, demonstrating previously undescribed heterogeneity within the ILC3 population. [Sci Signal] Abstract

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Vycellix’s CEO to Present Novel Approaches to Adoptive Cancer Immunotherapy
Vycellix, Inc., announced that its CEO, Evren Alici, M.D., Ph.D., will present a talk titled, “Screening for the Best Response for Adoptively Transferred NK-cells” and a half-day workshop titled, “Cell Expansion Methodologies for Enhanced Efficacy”. [Press release from Vycellix, Inc. discussing research to be presented at the Innate Killer Summit 2016, San Diego] Press Release

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Immunovaccine Launches DPX-NEO Program to Develop Patient-Specific Neoepitope Immunotherapies
Immunovaccine Inc. announced the launch of its DPX-NEO program to develop neoepitope immunotherapies to further expand the immuno-oncology applications for its DepoVax™-based vaccines. [Immunovaccine Inc.] Press Release

ImmunoCellular Therapeutics Receives Regulatory Approval in Canada, the UK and the Netherlands to Initiate ICT-107 Phase III Trial in Newly Diagnosed Glioblastoma
ImmunoCellular Therapeutics, Ltd. announced that the company has received approval from regulatory authorities in Canada, the United Kingdom and the Netherlands to initiate the ICT-107 Phase IIII registration trial in patients with newly diagnosed glioblastoma. [ImmunoCellular Therapeutics, Ltd.] Press Release

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