Immune Regulation News Volume 11.06 | Feb 22 2019

TOP STORY

β-Synuclein-Reactive T Cells Induce Autoimmune CNS Grey Matter Degeneration

Researchers showed that, in Lewis rats, T cells directed against the neuronal protein β-synuclein specifically invaded the grey matter and that this was accompanied by the presentation of multifaceted clinical disease. The expression pattern of β-synuclein induced the local activation of these T cells and, therefore, determined inflammatory priming of the tissue and targeted recruitment of immune cells. [Nature] Abstract

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Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity

Scientists report that acetylation inhibited cyclic GMP-AMP synthase (cGAS) activation and that the enforced acetylation of cGAS by aspirin robustly suppressed self-DNA-induced autoimmunity. They found that cGAS acetylation on either Lys384, Lys394, or Lys414 contributed to keeping cGAS inactive. [Cell] Abstract | Graphical Abstract

Targeting DNA Damage Response Promotes Anti-Tumor Immunity through STING-Mediated T-Cell Activation in Small Cell Lung Cancer

The authors showed that targeting DNA damage response proteins, poly ADP-ribose polymerase and checkpoint kinase 1 significantly increased protein and surface expression of PD-L1. [Cancer Discov] Abstract

The Transcription Factor c-Myb Regulates CD8⁺ T Cell Stemness and Antitumor Immunity

Investigators found that the transcription factor c-Myb was essential for generating and maintaining stem cells in the CD8⁺ T cell memory compartment. Following viral infection, CD8⁺ T cells lacking Myb underwent terminal differentiation and generated fewer stem cell-like central memory cells than did Myb-sufficient T cells. [Nat Immunol] Abstract

Subsets of Exhausted CD8⁺ T Cells Differentially Mediate Tumor Control and Respond to Checkpoint Blockade

Exhausted CD8⁺ tumor-infiltrating lymphocytes (TILs) included a subpopulation of ‘progenitor exhausted’ cells that retained polyfunctionality, persisted long term and differentiated into ‘terminally exhausted’ TILs. [Nat Immunol] Abstract

STAT1 Signaling Shields T Cells from NK Cell-Mediated Cytotoxicity

Scientists showed that STAT1 enabled CD4⁺ T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination. Stat1^−/− T cells failed to expand and establish colitis in lymphopenic mice. [Nat Commun] Full Article

Inducing Cancer Indolence by Targeting Mitochondrial Complex I Is Potentiated by Blocking Macrophage-Mediated Adaptive Responses

The authors demonstrated that complex I (CI)-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize hypoxia inducible factor-1. Such an adaptive response was mediated by tumor associated macrophages, whose blockage improved the effect of CI ablation. [Nat Commun] Full Article

Targeting DDR2 Enhances Tumor Response to Anti-PD-1 Immunotherapy

RNA-seq and CyTOF analysis revealed higher CD8⁺ T cell populations in tumors with DDR2 depletion and those treated with dasatinib when either was combined with anti-PD-1 treatment. [Sci Adv] Full Article

IL-27 Confers a Protumorigenic Activity of Regulatory T Cells via CD39

Investigators found that tumor-infiltrating Tregs (Ti-Tregs) failed to up-regulate CD39 in mice lacking EBI3 subunit of IL-27 or IL-27Ra. Mixed bone marrow chimera and in vitro studies showed that IL-27 signaling in Tregs directly drove CD39 expression on Ti-Tregs in a STAT1-dependent, but STAT3- and T-bet-independent, manner. [Proc Natl Acad Sci USA] Abstract

Reactive Oxygen Species Modulate Macrophage Immunosuppressive Phenotype through the Up-Regulation of PD-L1

Researchers showed that macrophages acquired an immunosuppressive phenotype and increased the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine, and paclitaxel. [Proc Natl Acad Sci USA] Abstract

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Human FOXP3⁺ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer

The authors review recent progress in the understanding of human Treg cell heterogeneity and function. They discuss these findings within the context of concepts in Treg cell development and function derived from preclinical models and insight from approaches targeting Treg cells in clinical settings. [Immunity] Abstract

Orchestration between ILC2s and Th2 Cells in Shaping Type 2 Immune Responses

Scientists discuss recent advances in the understanding of how group 2 innate lymphoid cells (ILC2s) and type 2 T helper (Th2) cells orchestrate type 2 immune responses through direct and indirect interactions. [Cell Mol Immunol] Abstract

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

Alpine Immune Sciences Presents Preclinical ALPN-101 GvHD Data

Alpine Immune Sciences, Inc. announced it will present preclinical GvHD data from its ALPN-101 program. [Press release from Alpine Immune Sciences, Inc. discussing research to be presented at the 2019 Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR, Houston] Press Release

Morphic Therapeutic Enters into Integrin Research and Development Collaboration with Janssen

Morphic Therapeutic announced that it has entered into a research and development collaboration with Janssen Biotech, Inc. to discover and develop novel integrin therapeutics for patients with conditions not adequately addressed by current therapies. [Morphic Therapeutic] Press Release

Torque Announces Clinical Trial Collaboration with Merck

Torque announced that it has entered into a clinical trial collaboration agreement with Merck. [Torque Therapeutics] Press Release

Alkermes and Clovis Oncology Initiate Research Collaboration to Explore Combination Cancer Therapies

Alkermes plc and Clovis Oncology, Inc. announced that the companies have entered into a research collaboration to evaluate ALKS 4230, Alkermes’ investigational engineered interleukin-2 variant immunotherapy, in combination with rucaparib, Clovis’ marketed PARP inhibitor, and lucitanib, Clovis’ investigational tyrosine kinase inhibitor. [Alkermes plc] Press Release

Mallinckrodt Announces Interim Analysis Results for Therakos^® Platform Phase III Clinical Trial in Treatment of Pediatric Patients with Steroid Refractory Acute Graft-versus-Host Disease

Mallinckrodt Pharmaceuticals announced interim analysis results of its company-sponsored, Phase III, single-arm, open-label, multi-center study assessing the efficacy of treating steroid-refractory, acute graft-versus-host disease pediatric patients with UVADEX^® Sterile Solution in conjunction with the THERAKOS^® CELLEX^® Photopheresis system. [Mallinckrodt Pharmaceuticals] Press Release

AbbVie Announces New Drug Application Accepted for Priority Review by U.S. FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis

AbbVie has announced that the FDA has accepted for priority review its New Drug Application for upadacitinib for the treatment of adult patients with moderate to severe rheumatoid arthritis. [AbbVie] Press Release

Moldovan Mathematician among Academics Running in General Election

Several researchers, including one mathematician, are running for seats in Moldova’s parliament this month. They hope to depoliticize science, improve education and address high levels of brain drain in the small country of 3.5 million people. [Nature News] Editorial

Open-Access Pioneer Randy Schekman on Plan S and Disrupting Scientific Publishing

Nobel laureate Randy Schekman shook up the publishing industry when he launched the open-access journal eLife in 2012. Armed with millions in funding from three of the world’s largest private biomedical charities — the Wellcome Trust, the Max Planck Society and the Howard Hughes Medical Institute — Schekman designed the journal to compete with publishing powerhouses such as Nature, Science and Cell. [Nature News] Editorial

Foreign Governments Want to Boost Their Biotech Industries — So They’re Setting Up Shop in Boston

Cities and states around the corner and around the country have angled for years to set themselves up as the next Kendall Square, hoping to import some of the magic of Boston’s biotech hub and its job-creating economic engine. Increasingly, foreign governments are pushing for the same. [STAT News] Editorial

NEW ISCT 2019 Annual Scientific Meeting
May 29-June 1, 2019
Melbourne, Australia

NEW Keystone Symposia: Tuberculosis: Immunity and Immune Evasion
January 16-20, 2020
Santa Fe, New Mexico, United States

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

NEW Postdoctoral Fellow – Tumor Immunology (University of Maryland)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

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

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)

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

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