Immune Regulation News Volume 9.09 | Mar 10 2017

TOP STORY

Class IIa HDAC Inhibition Reduces Breast Tumors and Metastases through Anti-Tumor Macrophages

Scientists utilized a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumor microenvironment and reduces tumor burden and pulmonary metastases by modulating macrophage phenotypes. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Rescue of Exhausted CD8 T Cells by PD-1–Targeted Therapies is CD28-Dependent

The authors demonstrated that the CD28/B7 costimulatory pathway is essential for effective programmed cell death-1 (PD-1) therapy in tumor-bearing mice and during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. [Science] Abstract | Press Release

T Cell Costimulatory Receptor CD28 Is a Primary Target for PD-1–Mediated Inhibition

By titrating programmed death-1 (PD-1) signaling in a biochemical reconstitution system, investigators demonstrated that the co-receptor CD28 is strongly preferred over the T cell receptor (TCR) as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. They also showed that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. [Science] Abstract

CD40-Signaling Abrogates Induction of RORγt⁺ Treg Cells by Intestinal CD103⁺ DCs and Causes Fatal Colitis

Researchers showed CD40-signaling as a microbe-independent signal that can induce migration of CD103⁺ DCs from the lamina propria to the mesenteric lymph nodes. [Nat Commun] Full Article

ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment

Investigators identified a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. [Cell Rep] Full Article | Press Release | Graphical Abstract

Cytoskeletal Adaptivity Regulates T Cell Receptor Signaling

Scientists asked whether the actin cytoskeleton governs differences in signaling in effector T cells versus naïve (unstimulated) T cells. Using atomic force microscopy and quantitative confocal microscopy, they found that naïve T cells had a mechanically stiffer cortical cytoskeleton than that of effector cells, which resulted in naïve cells forming smaller immune synapses with antigen-presenting cells. [Sci Signal] Abstract | Press Release

Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway

Researchers investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. They found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. [Sci Rep] Full Article

Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses

To test how human B cells may contribute to fungal-associated human T cell responses, the authors developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induce Candida albicans–associated, MHC class II–restricted responses of naive T cells. [J Immunol] Abstract

Hypoxia Enhances Immunosuppression by Inhibiting CD4⁺ Effector T Cell Function and Promoting Treg Activity

Researchers observed severe hypoxia in the colon of mice suffering from colitis-associated colon cancer that was accompanied by a reduced differentiation of CD4⁺ effector T cells and an enhanced number and suppressive activity of regulatory T cells. [Cell Physiol Biochem] Full Article

Interleukin 2 and Interleukin 10 Function Synergistically to Promote CD8⁺ T Cell Cytotoxicity, which Is Suppressed by Regulatory T Cells in Breast Cancer

Upon prolonged TCR stimulation, peripheral blood CD8⁺ T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of interleukin (IL)-2 and/or IL-10. The cytotoxicity of TCR-activated CD8⁺ T cells was also enhanced by exogenous IL-2 and/or IL-10. [Int J Biochem Cell Biol] Abstract

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Immunoregulatory Properties of the Cytokine IL-34

The authors recapitulate the most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in humans. [Cell Mol Life Sci] Abstract

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

Deciphera Pharmaceuticals Initiates a Phase I Clinical Trial of DCC-3014

Deciphera Pharmaceuticals announced that it has initiated a multi-center Phase I clinical trial of DCC-3014, a highly-selective small molecule CSF1R inhibitor, in patients with advanced malignancies. [Deciphera Pharmaceuticals, LLC] Press Release

FDA Grants Orphan Drug Designation to Boehringer Ingelheim’s Investigational Anti-CD33 Monoclonal Antibody BI 836858 for Treatment of Myelodysplastic Syndromes

Boehringer Ingelheim announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to its anti-CD33 monoclonal antibody BI 836858 for the treatment of myelodysplastic syndromes. [Boehringer Ingelheim Pharmaceuticals, Inc. (PR Newswsire Association LLC.)] Press Release

Patchy Progress on Fixing Global Gender Disparities in Science

Although women are publishing more studies, being cited more often, and securing more coveted first-author positions than they were in the mid 1990s, overall progress towards gender parity in science varies widely by country and field. This is according to a massive report released on 8^th March that is the first to examine such a broad swath of disciplines and regions of the world over time. [Nature News] Editorial

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who laboured to collect them. [Nature News] Editorial

NEW Keystone Symposium: Integrating Metabolism and Immunity
May 29-June 2, 2017
Dublin, Ireland

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

NEW Postdoctoral Position – Translational Immunology (German Cancer Research Center)

NEW PhD Student Position – Mucosal Immunology (Karolinska Institutet)

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

Postdoctoral Position(s) – HIV-1 Research (Aarhus University)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Postdoctoral Researcher – Development of Immune System (Lund University)

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

Associate/Full Professor – Immunobioengineering (University of Toronto)

Scientist – Immunology (Moderna Therapeutics)

Postdoctoral Fellow – Immunology (Institute of Molecular and Cell Biology)

Senior Scientist – (Immatics Biotechnologies GmbH)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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

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