Human Immunology News Volume 5.12 | Mar 28 2017

TOP STORY

Blocking the Recruitment of Naive CD4⁺ T Cells Reverses Immunosuppression in Breast Cancer

The authors showed that tumor-infiltrating naive CD4⁺ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. [Cell Res] Full Article

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IL-21 Restricts T Follicular Regulatory T Cell Proliferation through Bcl-6 Mediated Inhibition of Responsiveness to IL-2

The number of interleukin (IL)-2-dependent FoxP3⁺ regulatory T cells was increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor. [Nat Commun] Full Article

Activin-A Co-Opts IRF4 and AhR Signaling to Induce Human Regulatory T Cells that Restrain Asthmatic Responses

Investigators showed that the cytokine activin-A instructs the generation of CD4⁺ T cells that express the type 1 regulatory T-cell–associated molecules IL-10, inducible T-cell costimulator, lymphocyte activation gene 3 protein, and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells. [Proc Natl Acad Sci USA] Abstract

IL-1β Induced HIF-1α Inhibits the Differentiation of Human FOXP3⁺ T Cells

Scientists observed that IL-1β significantly reduced the frequency of FOXP3⁺ T cells under inducible regulatory Treg-polarizing conditions. Mechanistically, they showed that IL-1β activated mTORC1 and downstream upregulated hypoxia inducible factor-1 (HIF-1α) expression. [Sci Rep] Full Article

CD8⁺ T Cells Specific for the Islet Autoantigen IGRP Are Restricted in Their T Cell Receptor Chain Usage

Using single cell T cell receptor sequencing of CD8⁺ T cells specific for the IGRP265-273 epitope, the authors examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8⁺ T cell repertoires. [Sci Rep] Full Article

Prime-Boost Immunization Eliminates Metastatic Colorectal Cancer by Producing High-Avidity Effector CD8⁺ T Cells

Researchers examined a DNA and adenovirus (Ad5) combination regimen targeting guanylyl cyclase C, a receptor expressed by intestinal mucosa and universally expressed by metastatic colorectal cancer. DNA immunization efficacy was optimized by i.m. delivery via electroporation, yet it remained modest compared with Ad5. [J Immunol] Abstract

Antigen-Presenting Human γδ T Cells Promote Intestinal CD4⁺ T Cell Expression of IL-22 and Mucosal Release of Calprotectin

Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4⁺ T cells obtained from human blood or the colon. The potency of blood and intestinal γδ T-APCs was compared with that of monocytes and dendritic cells by assessing CD4⁺ T cell phenotypes and proliferation as well as cytokine and transcription factor profiles. [J Immunol] Abstract | Full Article

Genome-Wide Expression Profiling Establishes Novel Modulatory Roles of Vitamin C in THP-1 Human Monocytic Cell Line

Researchers performed a genome-wide temporal gene expression and functional enrichment analysis of THP-1 cells treated with 100 μM of vitamin C (vit C), a physiologically relevant concentration of the vitamin. Modulatory effects of vit C on THP-1 cells were revealed by differential expression of genes starting from eight hours onwards. [BMC Genomics] Full Article

Death Receptor 3 Signaling Enhances Proliferation of Human Regulatory T Cells

Investigators showed that human regulatory T cells (Tregs) express death receptor 3 (DR3) and demonstrated DR3-mediated activation of p38, ERK and NFκB. DR3 stimulation enhanced Treg expansion ex vivo while retaining their suppressive capacity. [FEBS Lett] Abstract

Radiation-Induced Decrease of CD8⁺ Dendritic Cells Contributes to Th1/Th2 Shift

The authors investigated the changes of dendritic cell (DC) subsets after ionizing radiation and its relationship with Th1/Th2 immunity. They found a significant decrease of BDCA3⁺ DC in the blood of patients treated with radiotherapy. [Int Immunopharmacol] Abstract

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CAR T-Cell Therapy: Progress and Prospects

The authors summarize the long series of advances in the development of effective chimeric antigen receptor (CAR) vector since their initial development in the 1990s, and describe emerging approaches to design that promise to enhance and widen the human gene therapy relevance of CAR-T cell therapy in the future. [Hum Gene Ther Methods] Abstract

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

Parker Institute for Cancer Immunotherapy, Bristol-Myers Squibb and the Cancer Research Institute Announce Collaboration to Accelerate Immuno-Oncology Research

The Parker Institute for Cancer Immunotherapy, Bristol-Myers Squibb Company and the Cancer Research Institute (CRI) announced a multi-year clinical research collaboration to coordinate and rapidly initiate clinical Immuno-Oncology studies across the Parker Institute and CRI networks. [The Parker Institute for Cancer Immunotherapy] Press Release

Immune-Onc Therapeutics, Inc. Announces Licensing and Collaboration with Albert Einstein College of Medicine and Memorial Sloan Kettering Cancer Center to Develop Novel Cancer Immunotherapy

Immune-Onc Therapeutics, Inc. announced that it has entered into an exclusive worldwide license agreement with Albert Einstein College of Medicine and Memorial Sloan Kettering Cancer Center. [Immune-Onc Therapeutics, Inc.] Press Release

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

Playing No Trump at AAAS Policy Forum

The relationship between U.S. scientists and the Trump administration hit a new low after organizers of a major annual science policy conference were unable to find anyone willing to discuss the president’s priorities. [ScienceInsider] Editorial

NIH Enables Investigators to Include Draft Preprints in Grant Proposals

Researchers should feel free to include preprints, or draft manuscripts that haven’t yet been gone through peer review, as part of their applications when they seek funding from the Bethesda, Maryland–based National Institutes of Health (NIH), the agency announced. [ScienceInsider] Editorial

Data Check: NSF Sends Congress a Garbled Message on Misconduct Numbers

When a senior National Science Foundation (NSF) official told the House of Representatives science committee this month about a “significant rise in the number of substantive allegations” of research misconduct, her testimony set off alarm bells. Legislators from both parties were clearly disturbed by this trend, which had led to three dozen findings of misconduct a year, and asked what the Arlington, Virginia–based NSF was doing about it. [ScienceInsider] Editorial

NEW European Immunogenetics and Histocompatibility Conference (EFI)
May 30-June 2, 2017
Heidelberg, Germany

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

NEW Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Research Fellowship – Tumor Immunology (University of Oslo)

Postdoctoral Fellow – Stromal Tissues Imprinting of Immune Cell Function (AstraZeneca)

Postdoctoral Fellow – Immune-Oncology (Johnson and Johnson)

Postdoctoral Researcher – Development of Immune System (Lund University)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Postdoctoral Position – Interaction between the Immune System and Pancreatic Cancer (Cold Spring Harbor Laboratory)

Postdoctoral Fellow – Immune Regulation and Human Diseases (The Wistar Institute)

Bioinformatician – Immunology (KOTAI Biotechnologies, Inc.)

Scientist – Immunology (Moderna Therapeutics)

Research Scientist – CAR-T Start-Up (Leucid Bio)

Postdoctoral Fellow – Molecular Immunology (University of California San Diego School of Medicine)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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