Immune Regulation News Volume 11.10 | Mar 22 2019

TOP STORY

CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response

Researchers engineered tumor-targeted CAR T cells to constitutively express the immune-stimulatory molecule CD40 ligand and explored efficacy in different mouse leukemia/lymphoma models. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Interferon-λ Enhances Adaptive Mucosal Immunity by Boosting Release of Thymic Stromal Lymphopoietin

Scientists report that mice deficient in interferon-λ (IFN-λ) signaling exhibited impaired CD8⁺ T cell and antibody responses after infection with a live-attenuated influenza virus. [Nat Immunol] Abstract

Activation of Naïve CD4⁺ T Cells Re-Tunes STAT1 Signaling to Deliver Unique Cytokine Responses in Memory CD4⁺ T Cells

The authors found that phosphorylation of STAT1 in response to IL-6 was regulated by the tyrosine phosphatases PTPN2 and PTPN22 expressed in response to the activation of naïve CD4⁺ T cells. [Nat Immunol] Abstract

Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension

Expression of the neutrophil chemoattractant CXCL1 was upregulated in primary liver sinusoidal endothelial cells exposed to mechanical stretch, compared to unexposed cells. Intravital imaging of livers in control mice revealed sinusoidal complexes of neutrophils and platelets and formation of neutrophil extracellular traps after partial ligation of the suprahepatic inferior vena cava. [Gastroenterology] Abstract | Press Release

Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity

Investigators showed that in C. elegans, dietary restriction (DR) extended lifespan by modulating a conserved innate immunity pathway that was regulated by p38 signaling and the transcription factor ATF-7. Longevity from DR depended upon p38-ATF-7 immunity being intact but downregulated to a basal level. [Cell Metab] Abstract | Press Release | Graphical Abstract

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

Researchers explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a “weaning reaction”—that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. [Immunity] Abstract | Press Release | Graphical Abstract

Therapeutic Targeting of Macrophages Enhances Chemotherapy Efficacy by Unleashing Type I Interferon Response

Scientists showed that targeting tumor-associated macrophages by colony-stimulating factor-1 receptor blockade in the K14cre;Cdh1^F/F;Trp53^F/F transgenic mouse model for breast cancer stimulated intratumoral type I interferon signaling, which enhanced the anticancer efficacy of platinum-based chemotherapeutics. [Nat Cell Biol] Abstract

Gfi1b Regulates the Level of Wnt/β-Catenin Signaling in Hematopoietic Stem Cells and Megakaryocytes

The authors showed that Gfi1b formed complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 and CtBP1 and regulated Wnt/β-catenin-dependent gene expression. [Nat Commun] Full Article

CHK1 Dosage in Germinal Center B Cells Controls Humoral Immunity

Investigators showed that the DNA damage response regulator checkpoint kinase 1 (CHK1) was essential for germinal center B cell survival. Remarkably, effective antibody-mediated immunity relied on optimal CHK1 dosage. [Cell Death Differ] Abstract

γδ T Cells Modulate Myeloid Cell Recruitment but Not Pain During Peripheral Inflammation

Researchers showed that absence of γδT cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. [Front Immunol] Full Article

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Regulatory T Cell Adaptation in the Intestine and Skin

The authors discuss current understanding of T_reg cell adaptation in the intestine and skin, including unique phenotypes, functions and metabolic demands, and how increased knowledge of T_reg cells at barrier sites might guide precision medicine therapies. [Nat Immunol] Abstract

Targeting Tumor-Associated Macrophages in Cancer

Preclinical studies have identified crucial pathways regulating the recruitment, polarization, and metabolism of tumor-associated macrophages during tumor progression. Moreover, novel therapeutics targeting these pathways can indirectly stimulate cytotoxic T cell activation and recruitment, and synergize with checkpoint inhibitors, chemotherapy and/or radiation therapy in preclinical studies. [Trends Immunol] Abstract

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

aTyr Pharma Announces Poster Presentation

aTyr Pharma, Inc. announced that data from its successful pilot study with the University of Nebraska Medical Center will be presented. [Press release from aTyr Pharma, Inc. discussing research to be presented at the 2019 AACR Annual Meeting, Atlanta] Press Release

Neovacs to Present the Preclinical Results of Its Therapeutic Vaccine Candidate IL-4/IL-13 Kinoid

Neovacs announced the presentation of the preclinical results of its proof of concept in allergy with its new IL-4/IL-13 Kinoid therapeutic vaccine. [Press release from Neovacs discussing research to be presented at the Keystone Congress: “Origins of Allergic Disease: Microbial, Epithelial and Immune Interactions”, Tahoe City] Press Release

Enterome Announces Research Collaboration with Renowned US Cancer Institute Focused on New Microbiome-Derived Cancer Immunotherapy

Enterome SA has entered into a research and development collaboration with Dana-Farber Cancer Institute to evaluate and develop gut microbiome-derived antigens as potential cancer immunotherapies. [Enterome SA] Press Release

Abzena and Lipum AB Sign Integrated CMC Agreement to Produce a Novel Biologic for Autoimmune Inflammatory Diseases

Abzena announced it has signed an agreement to support an integrated CMC program with Lipum, a company developing treatments for chronic inflammatory diseases. [Abzena Ltd] Press Release

Aptevo Therapeutics Begins Phase I Clinical Trial of APVO210 a Novel Bispecific Antibody for the Treatment of Autoimmune and Inflammatory Diseases

Aptevo Therapeutics Inc. announced that it has commenced dosing in a Phase I clinical trial of APVO210, a novel bispecific antibody candidate built on Aptevo’s ADAPTIR™ therapeutic protein platform which is being developed to treat autoimmune and inflammatory diseases. [Aptevo Therapeutics Inc.] Press Release

Moleculin Announces First Patients Enrolled in Lymphoma Clinical Trial

Moleculin Biotech, Inc. announced that the first two patients have been enrolled in its European clinical trial of WP1220 for the topical treatment of cutaneous T-cell lymphoma. [Moleculin Biotech, Inc.] Press Release

IMV and Centre de Recherche du CHU de Québec-Université Laval Collaboration Awarded a CQDM Grant to Develop First-in-Class Dual Target T Cell Therapy in Bladder Cancer Based on IMV’s DPX Technology

IMV Inc. announced that Canadian bioresearch consortium CQDM has awarded a grant to a collaboration among IMV, Centre de recherche du CHU de Québec-Université Laval, and La Fondation du CHU de Québec. [IMV Inc.] Press Release

SFA Therapeutics Wins Second Key US Patent for Treatment of Chronic Liver Diseases

SFA Therapeutics announced approval of the second key US patent derived from its research & development program, which utilizes microbiome-derived metabolite small molecules as drugs to modulate the body’s anti-inflammatory and immune systems. [SFA Therapeutics (Business Wire, Inc.)] Press Release

Chinese-American Scientist Societies Fear Racial Profiling

In a strongly worded letter published in Science, a group of Chinese-American scientists voiced concern that recent proposals from the National Institutes of Health and FBI actions could lead to unjust targeting of ethnically Chinese scientists. [The Scientist] Editorial

Universities Spooked by Trump Order Tying Free Speech to Grants

US President Donald Trump is expected to issue an executive order on 21 March that would require universities to certify that they protect free speech or risk losing federal research funds. The order will apply to 12 research agencies, including the National Institutes of Health, the National Science Foundation, the Department of Energy and NASA, a White House official said. [Nature News] Editorial

NEW 5^th CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 25-28, 2019
Paris, France

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

NEW Postdoctoral Researcher – Innate Lymphoid Cell Biology (Karolinska Institutet)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immuno-Oncology (Georgetown Lombardi Comprehensive Cancer Center)

Faculty Position – Immunology (Fox Chase Cancer Center)

Research Fellow – Protective and Aberrant Immunity (Monash University)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Fellow – Tumor Immunology (University of Maryland)

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)

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

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