Human Immunology News Volume 6.04 | Jan 30 2018

TOP STORY

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

Scientists isolated more than 450 respiratory syncytial virus (RSV) fusion glycoprotein-specific antibodies from seven RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naive B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. [Immunity] Abstract | Graphical Abstract

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BATF-Dependent IL-7R^hiGM-CSF⁺ T Cells Control Intestinal Graft-versus-Host Disease

Investigators showed that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal graft-versus-host disease (GVHD) tissues. Studies in complete MHC-mismatched and minor histocompatibility-mismatched GVHD models revealed that BATF-expressing T cells were functionally indispensable for intestinal GVHD manifestation. [J Clin Invest] Full Article

Tumor Infiltrating BRAF^V600E-Specific CD4 T Cells Correlated with Complete Clinical Response in Melanoma

Researchers describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). Analysis of the specificity of TIL identified rare CD4 T cells specific for BRAF^V600E and diverse CD8 T cells reactive to non-mutated self-antigens. [J Clin Invest] Full Article

Gimap5-Dependent Inactivation of GSK3β Is Required for CD4⁺ T Cell Homeostasis and Prevention of Immune Pathology

Scientists showed that GTPase of immunity-associated protein 5 (Gimap5) is essential for the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell activation. They showed that a human patient with a GIMAP5 loss-of-function mutation has lymphopenia and impaired T cell proliferation in vitro that can be rescued with GSK3 inhibitors. [Nat Commun] Full Article | Press Release

Angiogenic Factor-Driven Inflammation Promotes Extravasation of Human Proangiogenic Monocytes to Tumors

The authors showed mechanisms of extravasation of human CD14^dimCD16⁺ patrolling and CD14⁺CD16⁺ intermediate proangiogenic monocytes (HPMo), using human tumor xenograft models and live imaging of transmigration. IFNγ promoted an increase of the chemokine CX3CL1 on vessel lumen, imposing continuous crawling to HPMo and making these monocytes insensitive to chemokines required for their extravasation. [Nat Commun] Full Article

Wide Expression and Significance of Alternative Immune Checkpoint Molecules, B7x and HHLA2, in PD-L1 Negative Human Lung Cancers

Scientists compared the expression and function of PD-L1 with alternative immune checkpoints, B7x and HHLA2. PD-L1 expression was identified in 25% and 31% of tumors in the discovery and validation cohorts, and was associated with higher stage and lymph node involvement. [Clin Cancer Res] Abstract

The Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through PD-L1

The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional co-activator and an oncogene in breast and lung cancer. Investigators performed a comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling. They identified the immune checkpoint molecule PD-L1 as a target of Hippo signaling. [Cancer Res] Abstract

Distinctive Expression of T Cell Guiding Molecules in Human Autoimmune Lymph Node Stromal Cells upon TLR3 Triggering

The authors investigated the ability of human lymph node stromal cells (LNSCs) derived from rheumatoid arthritis (RA), RA-risk and healthy individuals to sense and respond to pathogens. Human LNSCs cultured directly from freshly collected lymph node biopsies expressed TLR1–9 with exception of TLR7. [Sci Rep] Full Article

Direct Anti-Inflammatory Effects of Granulocyte Colony-Stimulating Factor (G-CSF) on Activation and Functional Properties of Human T Cell Subpopulations In Vitro

Scientists investigated the direct effects of human G-CSF on functionality of human T-cell subsets. Upon T-cell activation in vitro, G-CSF significantly and specifically enhanced the proportion of CD114⁺ T cells in central memory CD4⁺ T cell compartment. [Cell Immunol] Abstract

TLR7 Escapes X Chromosome Inactivation in Immune Cells

TLR7 is encoded by an X chromosome locus, and researchers examined whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males. Biallelic B lymphocytes from women displayed greater TLR7 transcriptional expression than the monoallelic cells, correlated with higher TLR7 protein expression in female than in male leukocyte populations. [Sci Immunol] Full Article | Editorial

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Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment

The authors provide a brief overview of dendritic cell (DC) function, describe mechanisms by which DC functions are disrupted by the tumor microenvironment, and highlight recent developments in DC cancer vaccines. [Trends Cancer] Abstract

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

Morphotek to Present Poster on CA125 Suppression of Humoral Immune Responses of Antibodies

Morphotek^®, Inc. announced that it presented the following poster: The Tumor-Shed Antigen CA125 Suppresses Humoral Immune Responses of IgG1, IgG3 and IgM-Type Antibodies. [Press release from Morphotek^®, Inc. discussing research presented at the 2018 American Society of Clinical Oncology-Society of Immunotherapy of Cancer (ASCO-SITC) Symposium, San Francisco] Press Release

Stand Up To Cancer Awards $11M Convergence Research Program Using AI to Investigate Immunotherapies

Stand Up To Cancer announced a “Convergence 2.0” research initiative that awards $11 million to seven multi-disciplinary research teams to investigate immune system response to cancers. [Stand Up To Cancer] Press Release

Be The Match BioTherapies Invests in Tmunity Therapeutics to Support Advancement of Next-Generation T Cell Immunotherapies

Be The Match BioTherapies^® announced that it has invested in Tmunity Therapeutics, a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T cell immunotherapy. [Be The Match BioTherapies^®] Press Release

Faced with Failing Antibiotics, Scientists Are Using Killer Viruses to Fight Superbugs

Patients in danger of dying from uncontrollable bacterial infections could find new allies: killer viruses known as phages. Armed with advances in DNA sequencing and artificial intelligence, a few startups are turning these natural enemies of bacteria into promising alternatives to antibiotics. [MIT Technology Review] Editorial

Computer Scientist to Lead French Research Giant; Interim Head Leaves Amid Misconduct Allegations

Computer scientist Antoine Petit, 57, is the new head of Europe’s largest research organization. There was an unusual twist to Petit’s appointment, however. A week before the official procedure ended, the French government named Petit interim president of the National Center for Scientific Research, a position that had been held by cell biologist Anne Peyroche since Fuchs’s departure. [ScienceInsider] Editorial

NEW World Immunotherapy Congress USA 2018
May 23-24, 2018
San Diego, California, United States

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

NEW Research Scientist – Oncology Research (MedImmune)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Senior/Laboratory Research Scientist – B Cells (The Francis Crick Institute)

Postdoctoral Researcher – Cellular and Molecular Immunology (Karolinska Institutet)

Postdoctoral Fellow – Immunology/Vascular/Stromal Biology (Hospital for Special Surgery and Weill Cornell Medicine)

Postdoctoral Position – Microbiology and Immunology (University of Maryland)

Head of Laboratory – Cancer Vaccines/Oncolytic Viruses (Boehringer Ingelheim)

Investigator – Immuno-Oncology (Bristol-Myers Squibb)

Scientist – Immuno-Oncology (Bristol-Myers Squibb)

Postdoctoral Fellow – Immune Surveillance (University of Massachusetts)

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