Immune Regulation News Volume 10.09 | Mar 9 2018

TOP STORY

IL-7 and CCL19 Expression in CAR-T Cells Improves Immune Cell Infiltration and CAR-T Cell Survival in the Tumor

Investigators engineered chimeric antigen receptor T (CAR-T) cells to express IL-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. [Nat Biotechnol] Abstract

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Selective Targeting of Engineered T Cells Using Orthogonal IL-2 Cytokine-Receptor Complexes

Researchers engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4⁺ and CD8⁺ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. [Science] Abstract | Editorial

Nociceptor Sensory Neurons Suppress Neutrophil and γδ T Cell Responses in Bacterial Lung Infections and Lethal Pneumonia

Scientists found that TRPV1⁺ nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1⁺-neuron ablation increased survival, cytokine induction, and lung bacterial clearance. [Nat Med] Abstract | Press Release

Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models

To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, researchers developed BAC transgenic mice expressing human TREM2 in microglia. They found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model. [Neuron] Abstract | Press Release

Cancer-Associated Fibroblasts Induce Antigen-Specific Deletion of CD8⁺ T Cells to Protect Tumor Cells

Scientists provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts sample, process and cross-present antigen, killing CD8⁺ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. [Nat Commun] Full Article

Chloroquine Modulates Antitumor Immune Response by Resetting Tumor-Associated Macrophages toward M1 Phenotype

Investigators showed that chloroquine, a proven anti-malarial drug, can function as an antitumor immune modulator that switches tumor-associated macrophages from M2 to tumor-killing M1 phenotype. [Nat Commun] Full Article

4-1BB Costimulation Induces T Cell Mitochondrial Function and Biogenesis Enabling Cancer Immunotherapeutic Responses

4-1BB costimulation of CD8⁺ T cells resulted in enhanced mitochondrial capacity and engaged PGC1α-mediated pathways via activation of p38-MAPK. 4-1BB treatment of mice improved metabolic sufficiency in endogenous and adoptive therapeutic CD8⁺ T cells. [J Exp Med] Abstract | Press Release | Graphical Abstract

Characterization and Allergic Role of IL-33-Induced Neutrophil Polarization

The authors defined the characteristics of IL-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. [Cell Mol Immunol] Abstract

Lymphatic Endothelial Cells Regulate B-Cell Homing to Lymph Nodes via a NIK-Dependent Mechanism

Researchers showed that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells to regulate B-cell homing to lymph nodes. [Cell Mol Immunol] Abstract

RORα-Expressing T Regulatory Cells Restrain Allergic Skin Inflammation

Using two distinct mouse models of atopic dermatitis, investigators showed that expression of retinoid-related orphan receptor α (RORα) in skin-resident Tregs is important for restraining allergic skin inflammation. In both models, targeted deletion of RORα in mouse Tregs led to exaggerated eosinophilia driven by IL-5 production by type 2 innate lymphoid cells and T helper 2 cells. [Sci Immunol] Full Article | Press Release

Immune Evasion Mediated by PD-L1 on Glioblastoma-Derived Extracellular Vesicles

Scientists showed that glioblastoma extracellular vesicles (EVs) block T cell activation and proliferation in response to T cell receptor stimulation. Programmed death ligand-1 (PD-L1) was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. [Sci Adv] Full Article | Press Release

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Transcriptional Regulation and Development of Regulatory T Cells

The authors discuss major discoveries, active study topics and remaining questions regarding Treg cell development. [Exp Mol Med] Full Article

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Aimmune Therapeutics Presents Results from the Positive, Pivotal Phase III PALISADE Trial of AR101 for Peanut Allergy

Aimmune Therapeutics, Inc. announced that the results of its pivotal Phase III PALISADE trial of AR101 for the treatment of peanut allergy were presented. [Press release from Aimmune Therapeutics, Inc. discussing research presented at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI)–World Allergy Organization (WAO) Joint Congress, Orlando] Press Release

MD Anderson and Berkeley Lights Launch Optera Therapeutics to Accelerate Development of Cell Therapies for Cancer

The University of Texas MD Anderson Cancer Center and Berkeley Lights, Inc. announced the launch of Optera Therapeutics Corp, a biopharmaceutical company developing cell therapies with scalable manufacturing solutions for cancer. [Berkeley Lights, Inc.] Press Release

Caladrius Biosciences Reports Interim Analysis for Phase II T-Rex Trial of CLBS03 for Type 1 Diabetes

Caladrius Biosciences, Inc. report results from the predetermined interim analysis in The Sanford Project: T-Rex Study, a prospective, randomized, placebo-controlled, double-blind Phase II clinical trial of 110 patients to evaluate the safety and efficacy of the company’s CLBS03 as a treatment for recent-onset type 1 diabetes. [Caladrius Biosciences, Inc.] Press Release

Compugen Has Licensed Selexis’ Cell Line-Based Protein Expression Platform for the Development of Antibody-Based Therapeutics

Selexis SA announced that Compugen Ltd. has taken a license to the Selexis SUREtechnology Platform^™ for use in generating high-performance research cell banks. Compugen will leverage Selexis’ mammalian cell line-based protein expression platform to develop antibody-based therapeutics targeting certain cancers, including to support further advancement of COM701. [Selexis SA] Press Release

Scientists Win and Lose in Texas Primary Contests

Texas primary was the first test for scientists seeking seats in the U.S. House of Representatives, and the results were mixed. [ScienceInsider] Editorial

Behavioral ‘Violations’ Cost Prominent Neuroscientist Positions at Columbia, HHMI

Prominent Columbia University neuroscientist Tom Jessell, 66, has been fired for “serious [behavioral] violations” and the university is closing his lab, the New York City institution said in a statement. The Howard Hughes Medical Institute (HHMI) in Chevy Chase, Maryland, which effectively employed Jessell, a leader in understanding neural development, also terminated him as an investigator because he “violated HHMI policy,” according to a statement from the institute. [ScienceInsider] Editorial

Police Probe of Brazilian Marijuana Researcher Sparks Protests

A police investigation targeting Brazil’s most prominent marijuana researcher has ignited a wave of protest among scientists. They say that the move by authorities from the state of São Paulo threatens research freedoms at a time when science in the country faces severe problems because of draconian budget cuts. [Nature News] Editorial

NEW 23^rd Congress of European Hematology Association (EHA)
June 14-17, 2018
Stockholm, Sweden

Visit our events page to see a complete list of events in the community.

NEW Tenure Track Assistant Professor – Immune Signaling (Technical University of Munich)

NEW Scientist – Immunology (Bioverativ)

NEW Postdoctoral Fellow – Cardiovascular and Immunology Research (Icahn School of Medicine at Mount Sinai)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Professor – Translational Immunology (Rheinische Friedrich-Wilhelms-Universitat Bonn)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

Postdoctoral Scientist Opportunities – Biomedical Research (Cedars-Sinai)

Postdoctoral Fellowship – Immune Checkpoint Therapy (Canadian Nuclear Laboratories)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

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

Research Fellow Position – Immunology Research (ShanghaiTech University)

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