Human Immunology News Volume 7.26 | Jul 9 2019

TOP STORY

Connecting Blood and Intratumoral T_reg Cell Activity in Predicting Future Relapse in Breast Cancer

The signaling responsiveness of peripheral blood regulatory T (T_reg) II cells to immunosuppressive, T helper type 1 (T_H1) and T_H2 cytokines reflected intratumoral immunosuppressive potential, and predicted future relapse in two independent cohorts of patients with breast cancer. [Nat Immunol] Abstract | Press Release

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Epigenetic Programming Underpins B Cell Dysfunction in Human SLE

Researchers determined the DNA methylomes, chromatin accessibility profiles and transcriptomes from five human B cell subsets, including a newly defined effector B cell subset, from subjects with systemic lupus erythematosus (SLE) and healthy controls. [Nat Immunol] Abstract | Press Release

Notch-1 Inhibition Promotes Immune Regulation in Transplantation via Treg-Dependent Mechanisms

Scientists investigated the pattern of Notch-1 expression in effector and regulatory T cells (T_regs) in both murine and human recipients of a solid organ transplant. Using a selective human anti-Notch-1 antibody, they examined the effect of Notch-1 receptor inhibition in full MHC-mismatch murine cardiac and lung transplant models, and in a humanized skin transplant model. [Circulation] Abstract

NK Cells Switch from Granzyme B to Death Receptor-Mediated Cytotoxicity during Serial Killing

Investigators simultaneously measured the activities of granzyme B (GrzB) and caspase-8 in tumor cells upon contact with human natural killer (NK) cells. They observed that NK cells switched from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor-mediated killing during subsequent tumor cell encounters. [J Exp Med] Abstract | Graphical Abstract

Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo

The authors induced acute iron chelation in primary human macrophages and measured their transcriptional and metabolic responses. Acute iron deprivation caused an anti-proliferative Warburg transcriptome, characterized by an ATF4-dependent signature. [Cell Rep] Full Article | Graphical Abstract

Type I Interferon Therapy Limits CNS Autoimmunity by Inhibiting CXCR3-Mediated Trafficking of Pathogenic Effector T Cells

Using a T cell-transfer model of experimental autoimmune uveitis, scientists found that IFN-α/β treatment inhibited the migration of IFN-γ-producing pathogenic CD4⁺ T cells to effector sites. [Cell Rep] Full Article | Graphical Abstract

Impaired Memory B Cell Development and Antibody Maturation with a Skewing towards IgE in Patients with STAT3 Hyper-IgE Syndrome

To investigate the impact of STAT3 signaling on B cell responses, researchers assessed lymph node and bone marrow, blood B and plasma cell subsets, somatic hypermutations in Ig genes, in vitro proliferation and antibody production in STAT3‐HIES patients and healthy controls. [Allergy] Abstract

Circulating CXCR5⁻PD-1^hi Peripheral T Helper Cells Are Associated with Progression to Type 1 Diabetes

Circulating C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5⁻PD-1^hi) peripheral T helper (T_ph) cells shared several features associated with B cell helper function with circulating CXCR5⁻PD-1^hi follicular T helper cells. Moreover, the frequency of circulating T_ph cells was increased in children with newly diagnosed type 1 diabetes, especially in those who are positive for multiple autoantibodies. [Diabetologia] Full Article

High-Throughput Analysis of the Human Thymic Vδ1⁺ T Cell Receptor Repertoire

Investigators applied next-generation sequencing to analyse the γδ T cell receptor (γδTCR) repertoire of highly purified Vδ1⁺ T cells from human thymic biopsies. They revealed unsuspected aspects of thymically rearranged and expressed TRG and TRD genes, thus constituting a data resource that qualifies previous conclusions on the TCR repertoire of γδ T cells developing in the human thymus. [Sci Data] Full Article

Functional and Metabolic Impairment in Cigarette Smoke-Exposed Macrophages Is Tied to Oxidative Stress

Scientists studied the effects of cigarette smoke on model THP-1 and peripheral blood monocyte derived macrophages, and discovered a marked inhibition of bacterial phagocytosis which was replicated in primary human macrophages. [Sci Rep] Full Article

Human CD4⁺CD103⁺ Cutaneous Resident Memory T Cells Are Found in the Circulation of Healthy Individuals

Using tissue explant cultures, researchers found that CD4⁺CD69⁺CD103⁺ tissue-resident memory T cells in human skin could down-regulate CD69 and exit the tissue. [Sci Immunol] Full Article

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B Cell Signaling in Context

The authors describe the current view of the cellular consequences of B cell antigen receptor signaling and advances in the understanding of B cell signaling in context in vivo. [Nat Immunol] Abstract

T Follicular Helper Cells and T Follicular Regulatory Cells in Rheumatic Diseases

Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of T follicular helper (T_FH) cells that can be hyperactive, and also potentially have altered numbers of Tf regulatory (T_FR) cells with reduced function, suggesting a conceivable dysregulation in the balance between T_FH cells and T_FR cells in these diseases. [Nat Rev Rheumatol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Be The Match BioTherapies^® and Tmunity Announce Collaboration to Support Clinical Trials of Next-Generation Immunotherapies

Be The Match BioTherapies^® and Tmunity Therapeutics, Inc. announced a partnership to accelerate patient access to life-saving cell therapies. [BioTherapies^®] Press Release

Iovance Biotherapeutics Provides Cervical Cancer Program Updates following End of Phase II Meeting with FDA

Iovance Biotherapeutics, Inc. provided an update on the regulatory path for LN-145 in advanced cervical cancer. [Iovance Biotherapeutics, Inc. (GlobeNewswire, Inc.)] Press Release

Unum Therapeutics Announces Regulatory Update from Phase I Trial with ACTR087

Unum Therapeutics Inc. announced that the FDA has placed a clinical hold on the Phase I trial evaluating Unum’s ACTR087 in combination with rituximab following lymphodepleting chemotherapy with fludarabine and cyclophosphamide in patients with relapsed/refractory CD20⁺ B cell non-Hodgkin lymphoma. [Unum Therapeutics Inc. GlobeNewswire, Inc.)] Press Release

Alexion Receives FDA Approval Of SOLIRIS^® (Eculizumab) for the Treatment of Adults with Neuromyelitis Optica Spectrum Disorder (NMOSD) Who Are Anti-Aquaporin-4 (AQP4) Antibody Positive

Alexion Pharmaceuticals, Inc. announced that the FDA approved SOLIRIS^® for the treatment of NMOSD in adult patients who are AQP4 antibody positive. Approximately three quarters of all patients with NMOSD test positive for anti-AQP4 auto-antibodies. [Alexion Pharmaceuticals, Inc.] Press Release

Grifols Announces FDA Approval of Xembify^®, 20% Subcutaneous Immunoglobulin for Primary Immunodeficiencies

Grifols announced that Xembify^®, its new 20% subcutaneous immunoglobulin, has been approved by the FDA. [Grifols] Press Release

Hungarian Government Takes Control of Research Institutes despite Outcry

After months of struggle between Hungary’s research ministry and its scientific community, the nation’s parliament ratified a law on 2 July that gives the government control over the 40 or so institutes belonging to the Hungarian Academy of Sciences. The government says that its aim is to make research more innovative. [Nature News] Editorial

Mexican President Eases Up on Researchers’ Travel Rules

A month after announcing increased austerity measures on international travel for scientists, Mexico’s National Council of Science and Technology announced that at least one restriction would be loosened. Scientists would not require presidential approval for every trip abroad. [The Scientist] Editorial

NEW British Society for Immunology Congress 2019
December 2-5, 2019
Liverpool, United Kingdom

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

NEW Postdoctoral Position – Mucosal Immunology (University of California San Diego)

Postdoctoral Research Scientist – Molecular Immunology (Babraham Institute)

PhD Fellowship – Immunology (University of Oslo)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Fellow – Tumor Immunology (Massachusetts General Hospital and Harvard Medical School)

Senior Research Assistant – Immunology (MD Anderson Cancer Center)

Postdoctoral Fellow – Immunology (Boston University)

Researcher – Tumor Responses to Radiotherapy & Immunotherapy (University Hospital of Northern Norway)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

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

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