Immune Regulation News Volume 11.47 | Dec 13 2019

TOP STORY

An Intra-Tumoral Niche Maintains and Differentiates Stem-Like CD8 T Cells

Scientists investigated the requirements for maintaining a CD8 T cell response against human cancer. They found that CD8 T cells within tumors consist of distinct populations of terminally differentiated and stem-like cells. [Nature] Full Article | Editorial

(Ranked by impact factor of the journal)

Mutations that Prevent Caspase Cleavage of RIPK1 Cause Autoinflammatory Disease

Researchers showed that the heterozygous missense mutations D324N, D324H and D324Y prevented caspase cleavage of RIPK1 in humans and resulted in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy—a condition termed ‘cleavage-resistant RIPK1-induced autoinflammatory syndrome’. [Nature] Abstract

PD-1H (VISTA)-Mediated Suppression of Autoimmunity in Systemic and Cutaneous Lupus Erythematosus

The authors showed that mice lacking immune inhibitory receptor VISTA or programmed death-1 homolog (PD-1H) on a BALB/c background spontaneously developed cutaneous and systemic autoimmune diseases resembling human lupus. [Sci Transl Med] Abstract

Hair Eruption Initiates and Commensal Skin Microbiota Aggravate Adverse Events of Anti-EGFR Therapy

Investigators found that EGFR/ERK signaling was required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity and prevent the invasion of commensal microbiota and inflammatory skin disease. [Sci Transl Med] Abstract

Trained Immunity Modulates Inflammation-Induced Fibrosis

The authors showed the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviated fibrosis and inflammation in a mouse model of systemic sclerosis, whereas BCG-training exacerbated disease in this model. [Nat Commun] Full Article

miRNA142-3p Targets Tet2 and Impairs Treg Differentiation and Stability in Models of Type 1 Diabetes

Scientists showed that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interfered with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. [Nat Commun] Full Article

T Cell Receptor Specificity Drives Accumulation of a Reparative Population of Regulatory T Cells within Acutely Injured Skeletal Muscle

Tregs displaying the transgene-encoded T cell receptor (TCR) preferentially accumulated in injured hindlimb muscle in a TCR-dependent manner both in the straight transgenic model and in adoptive-transfer systems; non-Treg CD4⁺ T cells expressing the same TCR did not specifically localize in injured muscle. [Proc Natl Acad Sci USA] Abstract

Bach2 Deficiency Leads Autoreactive B Cells to Produce IgG Autoantibodies and Induce Lupus through a T Cell-Dependent Extrafollicular Pathway

Researchers examined the mechanism by which Bach2 regulated the development of systemic lupus erythematosus (SLE). Despite defects in Ig class switch recombination and germinal center formation when actively immunized, Bach2^−/− mice spontaneously accumulated IgG autoantibody-secreting cells without germinal center reactions in a regulatory T cell-independent manner, and this phenomenon was accompanied by manifestations akin to SLE. [Exp Mol Med] Full Article

Local Irradiation Sensitized Tumors to Adoptive T Cell Therapy via Enhancing the Cross-Priming, Homing, and Cytotoxicity of Antigen-Specific CD8 T Cells

The authors used transgenic OT-I/CD45.2/Rag^−/− mice as a source of effector CD8 T cells to determine whether irradiation combined with adoptive T cell transfer therapy could improve T cell proliferation and effector function in murine tumor models. [Front Immunol] Full Article

Clec10a Regulates Mite-Induced Dermatitis

Using whole-exome sequencing, researchers found that NC/Nga mice carried a stop-gain mutation in Clec10a, which encodes a C-type lectin receptor, Clec10a. The repair of this gene mutation using the CRISPR-Cas9 system ameliorated house dust mite (HDM)-induced dermatitis, indicating that the Clec10a mutation is responsible for hypersensitivity to HDM in NC/Nga mice. [Sci Immunol] Full Article

T Cell-Derived Interferon-γ Programs Stem Cell Death in Immune-Mediated Intestinal Damage

The authors found that stem cell compartment injury is a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing intestinal stem cells and impairing their recovery in T cell-mediated injury models. [Sci Immunol] Full Article

PAK4 Inhibition Improves PD-1 Blockade Immunotherapy

Scientists showed that p21-activated kinase 4 (PAK4) was enriched in non-responding tumor biopsies with low T cell and dendritic cell infiltration. In mouse models, genetic deletion of PAK4 increased T cell infiltration and reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. [Nat Cancer] Full Article

Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News.

How the Aging Microenvironment Influences Tumor Progression

Investigators address the role of the aging microenvironment in the promotion of tumor progression. Specifically, they discuss the cellular and molecular changes in non-cancerous cells during aging, and how these may contribute towards a tumor permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. [Nat Rev Cancer] Abstract

The Activation of Bystander CD8⁺ T Cells and Their Roles in Viral Infection

The authors address the induction of bystander CD8⁺ T cells, their effector functions, and their potential roles in immunity to infection, immunopathology, and autoimmunity. [Exp Mol Med] Abstract

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

Seven and Eight BioPharmaceuticals, Inc. Announces Clinical Collaboration to Evaluate BDB001 in Combination with KEYTRUDA^® (pembrolizumab) in Patients with Advanced Solid Tumors

Seven and Eight BioPharmaceuticals Inc. announced that it has signed a clinical research collaboration agreement with Merck, through a subsidiary, to explore the combination of Seven and Eight’s BDB001, an immune modulator targeting toll-like receptors 7 and 8, and Merck’s anti-PD-1 therapy, KEYTRUDA^® in treating patients with advanced solid tumors. [Seven and Eight BioPharmaceuticals Inc. (Business Wire, Inc.)] Press Release

Samyang Biopharm USA, Inc. and Talix Therapeutics NV Announce Global Strategic Collaboration to Advance Novel Immuno-Oncology Therapeutic

Samyang Biopharm USA, Inc. a global biotech subsidiary of the Samyang Pharmaceuticals Corp. announced that the company has entered into a research collaboration with the exclusive option to a worldwide licensing agreement with Talix Therapeutics NV. [Samyang Biopharm USA, Inc. (Business Wire, Inc.)] Press Release

ImaginAb Initiates Phase II Clinical Trial at Penn Medicine

ImaginAb, Inc. announced it has initiated its Phase II clinical trial of its lead product, CD8 tracer 89Zr-Df-IAB22M2C, at Penn Medicine. [ImaginAb, Inc.] Press Release

Viela Bio Announces Initiation of Phase IIb Trial of VIB4920 in Sjögren’s Syndrome

Viela Bio announced that the first patient has been dosed in a Phase IIb trial of VIB4920 for the treatment of Sjögren’s syndrome—a chronic, systemic autoimmune disease involving inflammation and destruction of the salivary and lacrimal glands which leads to severe dryness and chronic pain. [Viela Bio (GlobeNewswire, Inc.)] Press Release

aTyr Pharma Announces Positive Interim Safety Results from Ongoing Phase Ib/IIa Clinical Trial of ATYR1923

aTyr Pharma, Inc. announced the results of a pre-planned, blinded interim analysis of safety and tolerability, the primary endpoint of its ongoing Phase Ib/IIa clinical trial of its lead therapeutic candidate, ATYR1923, in patients with pulmonary sarcoidosis. [aTyr Pharma, Inc.] Press Release

BioInvent and Transgene Announce Compelling Preclinical Data for BT-001 in Solid Tumors

BioInvent International AB and Transgene announced compelling results from extensive in vitro and in vivo preclinical studies with BT-001, an oncolytic virus expressing an anti-CTLA4 antibody and the cytokine GM-CSF. [BioInvent International AB] Press Release

Kite Submits Biologics License Application to US Food and Drug Administration for Company’s Second CAR T Cell Therapy

Kite announced that it has submitted a Biologics License Application to the FDA for the investigational chimeric antigen receptor (CAR) T cell therapy, KTE-X19, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma. [Kite] Press Release

UK Election Dashes Scientists’ Hopes of Staying in the EU

The United Kingdom is now firmly on the path towards leaving the European Union, after the Conservative party won a majority of 79 seats in yesterday’s general election – a result that has major implications for science. [Nature News] Editorial

United States Drops Charges against Two More Scientists after Iran Prisoner Swap

US authorities have dropped charges against two researchers accused of attempting to export chemicals to Iran in violation of trade sanctions. The decision follows a prisoner swap in which the United States freed a third researcher who was charged alongside them – and imprisoned. [Nature News] Editorial

NEW Emerging Cellular Therapies: Cancer and Beyond and Engineering the Genome
February 8-12, 2020
Banff, Alberta, Canada

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

NEW Tenure Track Position – Genetics/Genomics/Pharmacogenomics of Immune Function in Disease (University of Kentucky)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Postdoctoral Scholar Position – Molecular Biology, Immunology and Synthetic Biology (University of California, Irvine)

PhD Studentship – Visualizing Immune Cell Activation at Single Molecule Resolution (Max Planck Institute for Infection Biology)

Postdoctoral Research Fellow – Immunology (Columbia University)

Research Assistant/Associate – Innate Immunity (Newcastle University)

Postdoctoral Fellow Positions – Computational Immunology/Biology (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellowship – Genetic Mechanisms of Lupus (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Cancer Immunology/Bioengineering (West Virginia University)

Postdoctoral Position – Pro-Inflammatory B Cells (Institut Necker Enfants Malades)

Postdoctoral Researcher – CAR T-Cell Immunology (Washington University School of Medicine)

Postdoctoral Research Fellow – Neuro-Immune Control of Metabolism (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.

Have we missed an important article or publication in Immune Regulation News? Click here to submit!

Comments or suggestions? Submit your feedback here.