Immune Regulation News Volume 10.20 | Jun 1 2018

TOP STORY

‘Hidden’ Driver Discovered that Helps Prime the Anti-Tumor Immune Response

Like exposing a crime boss whose authority has gone undetected, scientists have identified a hidden driver that influences production of the T cells that fight cancer and infections. [Press release from St. Jude Children’s Research Hospital discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Gut Microbiome-Mediated Bile Acid Metabolism Regulates Liver Cancer via NKT Cells

A selective increase of hepatic CXCR6⁺ natural killer T (NKT) cells was observed, independent of mouse strain, gender, or presence of liver tumors. The accumulated hepatic NKT cells showed an activated phenotype and produced more interferon-γ upon antigen stimulation. [Science] Abstract | Press Release | Graphical Abstract

CAR T Cell-Induced Cytokine Release Syndrome Is Mediated by Macrophages and Abated by IL-1 Blockade

Scientists report a murine model of cytokine release syndrome that develops within two-three days of chimeric antigen receptor (CAR) T cell infusion and that is potentially lethal and responsive to interleukin-6 receptor blockade. [Nat Med] Abstract

Monocyte-Derived IL-1 and IL-6 Are Differentially Required for Cytokine-Release Syndrome and Neurotoxicity Due to CAR T Cells

Scientists described a mouse model recapitulating key features of cytokine-release syndrome (CRS) and neurotoxicity. In humanized mice with high leukemia burden, chimeric antigen receptor-modified T (CAR T) cell-mediated clearance of cancer triggered high fever and elevated IL-6 levels, which are hallmarks of CRS. [Nat Med] Abstract

Testosterone Is an Endogenous Regulator of BAFF and Splenic B Cell Number

Investigators showed that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. [Nat Commun] Full Article

Induction of Anergic or Regulatory Tumor-Specific CD4⁺ T Cells in the Tumor-Draining Lymph Node

The authors showed, using a genetically engineered lung adenocarcinoma mouse model, that naive tumor-specific CD4⁺ T cells are activated and proliferate in the tumor-draining lymph node but do not differentiate into effectors or accumulate in tumors. [Nat Commun] Full Article

Potent and Selective Antitumor Activity of a T Cell-Engaging Bispecific Antibody Targeting a Membrane-Proximal Epitope of ROR1

To explore the therapeutic utility of T cell-engaging bispecific antibodies targeting the receptor tyrosine kinase ROR1, which is expressed by tumor cells of various hematologic and solid malignancies, researchers used a bispecific ROR1 × CD3 scFv-Fc format based on a heterodimeric and aglycosylated Fc domain designed for extended circulatory t_1/2 and diminished systemic T cell activation. [Proc Natl Acad Sci USA] Abstract | Press Release

Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability

Researchers showed that equilibrative nucleoside transporter 3 is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells. [Cell Rep] Full Article | Graphical Abstract

Neutrophils Provide a Favorable IL-1-Mediated Immunometabolic Niche that Primes GLUT4 Translocation and Performance in Skeletal Muscles

Scientists find mechanistic interactions between working skeletal muscles and locally recruited neutrophils expressing IL-1β, which supports muscle performance through priming exercise-dependent GLUT4 translocation. [Cell Rep] Full Article | Graphical Abstract

Generation of TCR-Expressing Innate Lymphoid-Like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-Leukemic Cell Response

iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells conditioned by CD4-modified CD40L^high iPS-T cells stimulated WT1-specific cytotoxic T lymphocyte priming, which eliminated WT1 peptide-expressing chronic myelogenous leukemia cells in vitro and in vivo. [Stem Cell Reports] Full Article | Graphical Abstract

Post-Transcriptional Regulator Rbm47 Elevates IL-10 Production and Promotes the Immunosuppression of B Cells

Scientists demonstrated that the overexpression of Rbm47 enabled B cells to facilitate Foxp3⁺ regulator T-cell induction and reduce the severity of DSS-induced ulcerative colitis. [Cell Mol Immunol] Full Article

Critical Role of OX40 in the Expansion and Survival of CD4 T-Cell-Derived Double-Negative T Cells

The authors demonstrated that the OX40 molecule was highly expressed on CD4⁻CD8⁻ double negative (cDNT). The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. [Cell Death Dis] Full Article

Treatment of T1D via Optimized Expansion of Antigen-Specific Tregs Induced by IL-2/Anti-IL-2 Monoclonal Antibody Complexes and Peptide/MHC Tetramers

Researchers devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific regulatory T cell (Treg) and maintain them over extended time periods. [Sci Rep] Full Article

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Antigen-Specific Regulatory T-Cell Responses against Aeroantigens and Their Role in Allergy

Recent technological progress enabling the identification of antigen-specific effector and regulatory T cells has significantly contributed to the understanding of tolerance. The authors discuss the experimental evidence for the various tolerance mechanisms described. [Mucosal Immunol] Abstract

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

MD Anderson and Amgen Announce Collaboration to Accelerate Early-Stage Treatments for Leukemia, Myelodysplastic Syndromes, Multiple Myeloma, Small-Cell Lung and Other Small-Cell Cancers

The University of Texas MD Anderson Cancer Center and Amgen announced two multi-year collaboration agreements aimed at accelerating development of a variety of Amgen’s early-stage oncology therapies for patients with leukemia, myelodysplastic syndromes, multiple myeloma, small-cell lung cancer, and other non-lung cancers with small-cell histologies. [The University of Texas MD Anderson Cancer Center] Press Release

Syndax and Nektar Therapeutics Announce Immuno-Oncology Clinical Trial Collaboration

Syndax Pharmaceuticals, Inc. and Nektar Therapeutics announced a non-exclusive, clinical collaboration to evaluate the safety and efficacy of Nektar’s NKTR-214, a CD122-biased agonist, in combination with entinostat, Syndax’s oral, small molecule class 1 specific HDAC inhibitor, in patients with metastatic melanoma who have previously progressed on treatment with an anti-programmed death receptor-1 agent. [Syndax Pharmaceuticals, Inc.] Press Release

‘Right-to-Try’ Law Intended to Weaken the FDA, Measure’s Sponsor Says in Blunt Remarks

Sen. Ron Johnson, the author of the federal “right-to-try” law signed by President Trump this week, wants to make one thing clear: His new law is meant to weaken the FDA. “This law intends to diminish the FDA’s power over people’s lives, not increase it,” he wrote in a letter to Commissioner Scott Gottlieb. [STAT News] Editorial

China to Crack Down on Fraud in Scandal-Hit Scientific Research amid ZTE Wrangle

China has issued the first national guidelines to enforce academic integrity in scientific research and vowed to punish academics and institutes for misconduct such as plagiarism and fabrication of data. [South China Morning Post Publishers Ltd] Editorial

Sweden Commits to Open Science with New Open-Access Publishing Deal

Swedish researchers can now publish their articles in Frontiers’ Open Access journals through a simplified process that covers publishing fees, thanks to a national agreement announced between Frontiers and the National Library of Sweden, on behalf of the organizations participating in the Bibsam Consortium. [American Association for the Advancement of Science] Editorial

Europe’s Science Spending Set for Another Big Boost

On 7 June, the European Commission will lay out detailed plans for one of the biggest single research programs on the planet. Called Horizon Europe, the program could be worth €97.6 billion between 2021 and 2027, up from about €77 billion for the current seven-year program, Horizon 2020. Its influence, however, will go beyond size. [ScienceInsider] Editorial

The Science Candidates: Texas Runoff Loss Leaves Wilson With Bitter Taste

This year, ScienceInsider is following a number of candidates with science, technology, engineering, and math backgrounds as they run for a seat in the U.S. House of Representatives. In some districts, science candidates have ended up competing against each other for the right to represent their party in the general election on 6 November. [ScienceInsider] Editorial

NEW American College of Allergy, Asthma, & Immunology (ACAAI) 2018 Annual Scientific Meeting
November 15-19, 2018
Seattle, Washington, United States

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

NEW PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

NEW PhD Student Positions – Immunology (Multiple Locations)

NEW Research Officer – Immunology (The Walter and Eliza Hall Institute of Medical Research)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Immunology (Uppsala University)

Postdoctoral Research Scientist – Immunology (Lilly)

Postdoctoral Fellowship – Immunology (University of South Carolina)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (Vlaams Instituut voor Biotechnologie)

Postdoctoral Researcher in Immunology/Vaccinology (Karolinska Institutet)

Postdoctoral Fellow – Immunology (Boston University School of Medicine)

Postdoctoral Fellow – Innate Immune Signaling (Houston Methodist Research Institute)

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

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

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