Immune Regulation News Volume 11.05 | Feb 15 2019

TOP STORY

Neoadjuvant Anti-PD-1 Immunotherapy Promotes a Survival Benefit with Intratumoral and Systemic Immune Responses in Recurrent Glioblastoma

The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells

Scientists generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. [Cancer Cell] Abstract | Graphical Abstract

Serine Metabolism Supports Macrophage IL-1β Production

Researchers found that in macrophages, serine was required for optimal lipopolysaccharide induction of IL-1β mRNA expression, but not inflammasome activation. The mechanism involved a requirement for glycine, which is made from serine, to support macrophage glutathione synthesis. [Cell Metab] Abstract | Graphical Abstract

Human Fetal TNF-α-Cytokine-Producing CD4⁺ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

The authors demonstrated that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)⁺CD4⁺CD69⁺ T effector memory cells. Single-cell RNA sequencing of fetal intestinal CD4⁺ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. [Immunity] Abstract | Graphical Abstract

Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8⁺ T Cell Responses

Investigators showed that CD19⁺ extracellular vesicles from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8⁺ T cell responses. [Immunity] Abstract | Graphical Abstract

MicroRNA-142-Mediated Repression of Phosphodiesterase 3B Critically Regulates Peripheral Immune Tolerance

Scientists demonstrated that peripheral immune tolerance was critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acted as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. [J Clin Invest] Full Article

The Short-Chain Fatty Acid Pentanoate Suppresses Autoimmunity by Modulating the Metabolic-Epigenetic Crosstalk in Lymphocytes

Researchers showed that pentanoate, a physiologically abundant short-chain fatty acid, was a potent regulator of immunometabolism. Pentanoate induced IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. [Nat Commun] Full Article

PLCβ2 Negatively Regulates the Inflammatory Response to Virus Infection by Inhibiting Phosphoinositide-Mediated Activation of TAK1

The authors report that phospholipase C (PLC) β2 inhibited the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-β-activated kinase 1 (TAK1) activation. [Nat Commun] Full Article

IL-33/Regulatory T Cell Axis Triggers the Development of a Tumor-Promoting Immune Environment in Chronic Inflammation

Epidermis-derived interleukin (IL)-33 up-regulation and its induction of regulatory T cell accumulation in the skin preceded the transition from acute to chronic allergic contact dermatitis (ACD) and triggered the tumor-promoting immune environment in chronic ACD. [Proc Natl Acad Sci USA] Abstract | Press Release

Depletion of Regulatory T Cells in Tumors with an Anti-CD25 Immunotoxin Induces CD8 T Cell-Mediated Systemic Antitumor Immunity

Mice with complete regressions of 66c14 tumors were immune to rechallenge with 66c14 cells. Mice with complete regressions of AB1 or CT26M tumors developed cross-tumor immunity rejecting both tumor types. [Proc Natl Acad Sci USA] Abstract

Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation

Investigators established a transcriptional signature of central nervous system Treg cells that accumulate during experimental autoimmune encephalitis and identified a pathway that maintained Treg cell function and identity during severe inflammation. [Cell Rep] Full Article | Graphical Abstract

Autoantibody against β₁-Adrenoceptor Promotes the Differentiation of Natural Regulatory T Cells from Activated CD4⁺ T Cells by Up-Regulating AMPK-Mediated Fatty Acid Oxidation

In vitro, β₁-adrenoceptor promoted natural regulatory T cell cell differentiation by up-regulating mitochondrial fatty acid oxidation in activated CD4⁺ T cells via AMP-activated protein kinase (AMPK) activation and mitochondrial membrane potential reduction. [Cell Death Dis] Full Article

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The Evolving Landscape of Biomarkers for Checkpoint Inhibitor Immunotherapy

The authors discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumor genomics, host germline genetics, programmed cell death 1 ligand 1 levels and other features of the tumor microenvironment, as well as the gut microbiome. [Nat Rev Cancer] Abstract

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

Lilly Completes Acquisition of Loxo Oncology

Eli Lilly and Company announced the successful completion of its acquisition of Loxo Oncology, Inc.. The acquisition broadens the scope of Lilly’s oncology portfolio into precision medicines through the addition of a pipeline of highly selective potential medicines for patients with genomically defined cancers. [Eli Lilly and Company] Press Release

AbbVie and Teneobio Announce a Strategic Transaction to Develop a New Treatment for Multiple Myeloma

AbbVie, Teneobio, Inc. and its affiliate TeneoOne, Inc. announced that they have entered a global strategic transaction to develop and commercialize TNB-383B, a BCMA-targeting immunotherapeutic for the potential treatment of multiple myeloma. [AbbVie Inc.] Press Release

3SBio and Verseau Establish Global Clinical Development Collaboration for First-in-Class Immuno-Oncology Therapies

3SBio Inc. and Verseau Therapeutics, Inc. announced a partnership agreement focused on the development and commercialization of novel monoclonal antibodies in the field of immuno-oncology for a broad range of cancers. Verseau’s proprietary drug discovery platform generates first-in-class macrophage checkpoint modulators to benefit patients with cancer, immune and inflammatory diseases. [3SBio Inc.] Press Release

AmorChem Reinforces Its Innate Immunity Franchise with an Investment in Checkpoint Control Target SRSF3

AmorChem II announced the financing of a new university project. Following the agreement it has reached with Université Laval and the CERVO Brain Research Centre of the CIUSSS de la Capitale Nationale, the venture capital fund will finance the development of a project on the SRSF3 target in the laboratory of Dr Jasna Kriz. [AmorChem II (Business Wire, Inc.)] Press Release

IFM Therapeutics Launches New Subsidiary, IFM Due, to Advance cGAS/STING Antagonists for Serious Inflammatory and Autoimmune Diseases

IFM Therapeutics announced the launch of IFM Due, a subsidiary company developing a suite of cGAS inhibitors and STING antagonists that aim to block excessive production of interferon and other pro-inflammatory cytokines via the cGAS/STING pathway, which is known to drive a range of serious diseases. [IFM Therapeutics] Press Release

Hungary’s Scientists Outraged by Government Budget Grab

In the cold afternoon sunshine of 12 February, hundreds of scientists and their supporters formed a human chain around the historic Hungarian Academy of Sciences building in Budapest. The gesture was one of protection. Inside, academy members were holding an emergency meeting to decide how to handle what they say is a serious a threat to the nation’s science community. [Nature News] Editorial

Indian Payment-for-Papers Proposal Rattles Scientists

Indian scientists are criticizing a government proposal to pay graduate students who publish in select journals. They fear that it could degrade the quality of research and lead to an increase in scientific misconduct, by incentivizing publishing rather than good science. [Nature News] Editorial

NEW Gordon Research Conference: Phagocytes
June 2-7, 2019
Waterville Valley, New Hampshire, United States

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

NEW Research Officer – Immunotherapy for Brain Cancer (The Walter and Eliza Hall Institute of Medical Research)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Tumor Immune Evasion (Luxembourg Institute of Health)

Staff Scientist – Immunology (Cellzome GmbH)

Assistant Professor – Translational Cancer Research (Texas Tech University Health Sciences Center El Paso)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

Postdoctoral Fellow – Immunology (Yonsei Cancer Center)

Postdoctoral Fellowship – Cancer Immunology and Immunotherapy (Columbia Center for Translational Immunology)

Postdoctoral Scientist – Molecular Innate Immunity (Cedars-Sinai Medical Center)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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