Human Immunology News Volume 5.20 | May 23 2017

TOP STORY

Normal and Cancerous Mammary Stem Cells Evade Interferon-Induced Constraint through the miR-199a–LCOR Axis

Scientists showed that miR-199a promotes stem cell properties in mammary stem cells and breast cancer stem cells by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem-cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. [Nat Cell Biol] Abstract | Press Release

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Notch-Mediated Conversion of Activated T Cells into Stem Cell Memory-Like T Cells for Adoptive Immunotherapy

Investigators show a strategy for generating stem cell memory T-like cells in vitro (iT_SCM cells) from activated CD4⁺ and CD8⁺ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lost PD-1 and CTLA-4 expression, and produced a large number of tumor-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy. [Nat Commun] Full Article

Anti-Platelet Factor 4/Polyanion Antibodies Mediate a New Mechanism of Autoimmunity

Researchers showed that antibodies with binding forces of approximately 60–100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-heparin-induced thrombocytopenia patients with binding forces ≥100 pN binds to platelet factor alone in the absence of polyanions. [Nat Commun] Full Article

Manipulating DNA Damage-Response Signaling for the Treatment of Immune-Mediated Diseases

Scientists found that activated mouse and human T cells display a pronounced DNA damage-response in vitro and in vivo. Upon screening a variety of small-molecule compounds, they found that potentiation of p53 (via inhibition of MDM2) or impairment of cell cycle checkpoints (via inhibition of CHK1/2 or WEE1) led to the selective elimination of activated, pathological T cells in vivo. [Proc Natl Acad Sci USA] Abstract | Press Release

CCR8⁺FOXp3⁺ T_reg Cells as Master Drivers of Immune Regulation

The authors identified CCR8⁺ regulatory T cells (T_reg cells) as drivers of immunosuppression. They showed that in human peripheral blood cells, more than 30% of T_reg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. [Proc Natl Acad Sci USA] Abstract

Functionally Diverse Human T Cells Recognize Non-Microbial Antigens Presented by MR1

In healthy individuals, researchers identified MR1-restricted T cells displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. [eLife] Full Article | Press Release

CECR1-Mediated Cross Talk between Macrophages and Vascular Mural Cells Promotes Neovascularization in Malignant Glioma

The effect of cat eye syndrome critical region protein 1 (CECR1) in macrophages on tumor angiogenesis was investigated. Immunohistochemical evaluation of glioblastoma multiforme tissue samples showed that the expression of CECR1 correlates with microvascular density in the tumors, confirming data from the TCGA set. In a three-dimensional co-culture system consisting of human pericytes, human umbilical vein endothelial cells and THP1-derived macrophages, CECR1 knockdown by siRNA and CECR1 stimulation of macrophages inhibited and promoted new vessel formation, respectively. [Oncogene] Full Article

Directed Differentiation of Human Pluripotent Stem Cells to Microglia

To improve the understanding of human microglial biology, scientists devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived and human primary microglia as well as clear distinctions from macrophages. [Stem Cell Reports] Full Article

CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma

Targeting GD2 on neuroblastoma (NB) with T cells expressing a 1^st generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. Researchers developed a 3^rd generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CART) would be safe and effective. This Phase I study enrolled relapsed/refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CART plus cyclophosphamide/fludarabine (Cy/Flu) and cohort 3 was treated with CART, Cy/Flu and a PD-1 inhibitor. [Mol Ther] Abstract

Kif4A Mediate the Accumulation and Reeducation of THP-1 Derived Macrophages via Regulation of CCL2-CCR2 Expression in Crosstalking with OSCC

Scientists showed that, the interaction between THP-1 derived macrophage and oral squamous cell carcinomas cell line Cal-27 may up-regulate the kinesin family member 4A (Kif4A) expression in both of them. Additionally, elevated soluble CCL2 in medium and more expression of CCR2 on macrophage were observed during the crosstalk. [Sci Rep] Full Article

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Modulators of Microglial Activation and Polarization after Intracerebral Hemorrhage

Researchers summarize key studies on modulators of microglial activation and polarization after intracerebral hemorrhage, including M1-like and M2-like microglial phenotype markers, transcription factors and key signaling pathways. [Nat Rev Neurol] Abstract

Hallmarks of Response to Immune Checkpoint Blockade

The authors describe the foundation for pillars and hallmarks of response to immune checkpoint blockade, with a discussion of their relevance to immune monitoring and mechanisms of resistance. [Br J Cancer] Full Article

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PCI Biotech and Rxi Pharmaceuticals Extend Research Collaboration to the Field of Immuno-Oncology

PCI Biotech and RXi Pharmaceuticals announced that they are extending their preclinical research collaboration. [PCI Biotech] Press Release

Aurinia Doses First Patient in AURORA Phase III Clinical Trial of Voclosporin in Lupus Nephritis

Aurinia Pharmaceuticals Inc. announced that the first patient has been dosed in AURORA, the company’s Phase III confirmatory clinical trial evaluating voclosporin for the treatment of lupus nephritis, an autoimmune disease caused by lupus that involves extreme inflammation and failure of the kidneys. [Aurinia Pharmaceuticals Inc.] Press Release

FDA Approves First Cancer Treatment for Any Solid Tumor with a Specific Genetic Feature

The U.S. Food and Drug Administration (FDA) granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker). This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated. [The U.S. Food and Drug Administration] Press Release

Sanofi and Regeneron Announce FDA Approval of Kevzara^® (Sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients

Sanofi and Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) approval of Kevzara^® for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drug. Kevzara is a human monoclonal antibody that binds to the interleukin-6 receptor (IL-6R), and has been shown to inhibit IL-6R mediated signaling. IL-6 is a cytokine in the body that, in excess and over time, can contribute to the inflammation associated with RA. [Sanofi] Press Release

Nanobiotix Announces First Positive Human Data Showing that NBTXR3 Could Become a Backbone in Immuno-Oncology

Nanobiotix announced its first set of clinical data from its immuno-oncology program, showing the potential ability of NBTXR3 to transform “cold” tumors into “hot” tumors. [Nanobiotix] Press Release

What’s in Trump’s 2018 Budget Request for Science?

President Donald Trump unveiled his full 2018 budget request to Congress. The spending plan, for the fiscal year that begins 1 October, fleshes out the so-called skinny budget that the White House released this past March. That plan called for deep cuts to numerous research agencies. [ScienceInsider] Editorial

UK Political Parties Promise Science Funding Boost

UK scientists worried about how Brexit will affect their funding received a boost when the country’s three main national parties pledged long-term targets to raise research spending. [Nature News] Editorial

Journal that Holds Record for Retracted Papers Also Has a Problem with Editorial Board Members

Last month, Springer, announced that the journal Tumor Biology was retracting 107 papers after finding that the peer-review process had been compromised. It was the third mass retraction at Tumor Biology. But that’s not Tumor Biology’s only problem. ScienceInsider has discovered that the journal’s editorial board, as published online, contains the names of several scientists who say they have no relationship whatsoever with the journal—including German Nobel laureate Harald zur Hausen. [ScienceInsider] Editorial

NEW Worldwide Innovative Networking in Personalized Cancer Medicine (WIN) 2017
June 26-27, 2017
Paris, France

NEW ICI 2018: 20^th International Conference on Immunology
September 14-17, 2017
London, England

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NEW Scientific Sales Representative – Cell Separation (STEMCELL Technologies Inc.)

NEW PhD Research Fellowship – Neuroimmunology (University of Oslo)

Postdoctoral Fellow – Innate and Adaptive Immunity (Stanford University)

Postdoctoral Position – Cancer Immunology and Immunotherapy (Weill Cornell Medicine)

Scientist – Analytical Development (KBI Biopharma)

Postdoctoral Research Associate – Molecular Microbiology and Immunology (University of Southern California)

Senior Scientific Researcher – Personalized Cancer Vaccines (Genentech)

Tenure-Track Faculty Position(s) – Immunology (Cornell University)

Faculty Position – Cancer Immunology (Mayo Clinic)

Postdoctoral Fellow – Innate Immunity and Neurodegeneration (Mount Sinai Health System)

Postdoctoral Associate Position – Immunometabolism and Myeloid Cell Regulation within the Tumor Microenvironment (University of Louisville Health Science Center)

Postdoctoral Scholar – Multiple Sclerosis (University of Washington)

Postdoctoral Research Fellow – Inflammation and Immuno-Oncology (Yale School of Medicine)

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

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