Immune Regulation News Volume 11.01 | Jan 18 2019

TOP STORY

Translation Control of the Immune Checkpoint in Cancer and Its Therapeutic Targeting

Scientists developed an in vivo mouse model of liver cancer to study oncogene cooperation in immunosurveillance. They showed that MYC overexpression synergized with KRAS^G12D to induce an aggressive liver tumor leading to metastasis formation and reduced mouse survival compared with KRAS^G12D alone. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins

Researchers report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not β2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. [Immunity] Full Article | Graphical Abstract | Editorial

Intratumoral Tcf1⁺PD-1⁺CD8⁺ T Cells with Stem-Like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy

Investigators identified a subset of tumor-reactive tumor-infiltrating CD8⁺ T lymphocytes (TILs) bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. Tcf1⁺PD-1⁺ TILs mediated the proliferative response to immunotherapy, generating both Tcf1⁺PD-1⁺ and differentiated Tcf1⁻PD-1⁺ cells. [Immunity] Abstract | Graphical Abstract

Expression of Novel Long Noncoding RNAs Defines Virus-Specific Effector and Memory CD8⁺ T Cells

The authors identified hundreds of unannotated long noncoding RNAs (lncRNAs) and showed that expression profiles of both known and novel lncRNAs were sufficient to define naive, effector, and memory CD8⁺ T cell subsets, implying that they may be involved in fate decisions during antigen-driven differentiation. [Nat Commun] Full Article

Breakdown of Adaptive Immunotolerance Induces Hepatocellular Carcinoma in HBsAg-tg Mice

Researchers showed that expression of TIGIT, a promising immune checkpoint in tumor immunotherapy, increased with age on hepatic CD8⁺ T cells in HBsAg-transgenic (HBs-tg) mice whose adaptive immune system is tolerant to HBsAg. [Nat Commun] Full Article

Rps14, Csnk1a1 and miRNA145/miRNA146a Deficiency Cooperate in the Clinical Phenotype and Activation of the Innate Immune System in the 5q- Syndrome

Macrophages, regulatory cells of erythropoiesis and the innate immune response, were significantly increased in Rps14/Csnk1a1/miR-145/146a deficient mice as well as in 5q- syndrome patient bone marrows and showed activation of the innate immune response, reflected by increased expression of S100A8, and decreased phagocytic function. [Leukemia] Abstract

Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8⁺ T Cells

Using a mouse model ubiquitously expressing β5t, the authors showed that aberrant expression of self-peptides generated by β5t affects CD8⁺ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8⁺ T cells. [Cell Rep] Full Article | Graphical Abstract

The P2X7 Receptor Modulates Immune Cells Infiltration, Ectonucleotidases Expression and Extracellular ATP Levels in the Tumor Microenvironment

The immune infiltrate of tumors growing in P2X7 null mice showed a decrease in CD8⁺ cells and an increased number of Tregs, overexpressing the fitness markers OX40, PD-1, and CD73. [Oncogene] Full Article

The Phytosphingosine-CD300b Interaction Promotes Zymosan-Induced, Nitric Oxide-Dependent Neutrophil Recruitment

Scientists determined the mechanisms underlying the zymosan-induced accumulation of neutrophils in mice. Loss of the receptor CD300b reduced the number of neutrophils recruited to dorsal air pouches in response to zymosan, but not in response to lipopolysaccharide, a bacterial membrane component recognized by Toll-like receptor 4. [Sci Signal] Abstract

Cadherin-11-Mediated Adhesion of Macrophages to Myofibroblasts Establishes a Profibrotic Niche of Active TGF-β

Investigators showed that homotypic cadherin-11 interactions promoted the specific binding of macrophages to and persistent activation of profibrotic myofibroblasts. Cadherin-11 was highly abundant at contacts between macrophages and myofibroblasts in mouse and human fibrotic lung tissues. [Sci Signal] Full Article

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Sodium in the Microenvironment Regulates Immune Responses and Tissue Homeostasis

During tissue inflammation, immune cells infiltrate the interstitial space of target organs, where they sense and adapt to local environmental stimuli. Such stimuli include not only pathogens but also local factors such as the levels of oxygenation, nutrients and electrolytes. [Nat Rev Immunol] Abstract

The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy

The authors summarize recent advances that have illuminated inhibitory checkpoints in natural killer (NK) cells, some of which are shared with conventional cytotoxic T lymphocytes. They also outline emerging approaches aimed at unleashing the potential of NK cells in immunotherapy. [Trends Immunol] Abstract

From Therapeutic Antibodies to Immune Complex Vaccines

In this review, both basic studies and experimental/clinical applications of immune complexes leading to the development of preventive and therapeutic vaccines are presented. [npj Vaccines] Full Article

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

Cue Biopharma Announces Presentation Highlighting Immuno-STAT Platform and CUE-101

Cue Biopharma, Inc. announced a poster presentation featuring pre-clinical data on its lead candidate CUE-101, an Immuno-STAT™ (Selective Targeting and Alteration of T cells) Biologic being developed for the treatment of HPV-associated cancers. [Press release from Cue Biopharma, Inc. discussing research to be presented at the Keystone Symposia Conference, Vancouver] Press Release

Innovent Announces First Patient Dosed in a Phase I Clinical Trial of Anti-CD47 Monoclonal Antibody

Innovent Biologics, Inc. announced that the first patient has been successfully dosed in a Phase I clinical trial of anti-CD47 monoclonal antibody for patients with advanced malignancies. [Innovent Biologics, Inc.] Press Release

ADC Therapeutics Announces First Patient Dosed in Phase I Clinical Trial of ADCT-601 in Advanced Solid Tumors

ADC Therapeutics announced that the first patient has been dosed in its Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-601 in patients with selected solid tumors that are locally advanced or metastatic. [ADC Therapeutics] Press Release

Omeros Finalizes with FDA Clinical Plan for OMS721 Approval in IgA Nephropathy

Omeros Corporation announced that it has finalized its clinical plan for OMS721 submission and approval in immunoglobulin A (IgA) nephropathy following a recent meeting with the FDA. [Omeros Corporation] Press Release

Crash-Out Brexit Looms Larger for Scientists after Deal Rejected

A historic defeat for U.K. Prime Minister Theresa May has raised the odds that the United Kingdom will crash out of the European Union in March, a prospect that scientists dread for its potential for disruption to research collaborations and the economy. [ScienceInsider] Editorial

German Institutions and Wiley Reach Open-Access Publishing Deal

Ater nearly three years of contract negotiations, a consortium of nearly 700 German libraries, research institutes, and universities called Project DEAL has forged an agreement with the scholarly publisher Wiley that moves the publishing industry towards more open access. [The Scientist] Editorial

How UK Scientists Are Planning for a Chaotic No-Deal Brexit

British scientists are ramping up preparations for a ‘no deal’ Brexit on 29 March — a situation that would instantly affect travel, data collection, clinical trials and crucial laboratory supplies. [Nature News] Editorial

NEW Keystone Symposia: Innate Immune Receptors: Roles in Immunology & Beyond
March 10-14, 2019
Taipei, Taiwan

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

NEW PhD Student – Oncolytic Virus Immune Therapy (German Cancer Research Center)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (Yonsei Cancer Center)

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

PhD Position – Epigenetics of Melanoma Immunotherapy Response (University of Otago)

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

Supervisor – Transfusion Medicine – Immune, Progenitor, & Cell Therapy (Mayo Clinic-Rochester)

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

Postdoctoral Fellow/Research Associate – Immunology (Turnstone Biologics Inc.)

Postdoctoral Position – Immunology (Ludwig-Maximilians-Universität)

Postdoctoral Position – Natural Killer Cells (The Scripps Research Institute)

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