Immune Regulation News Volume 9.25 | Jul 7 2017

TOP STORY

Skewing of the Population Balance of Lymphoid and Myeloid Cells by Secreted and Intracellular Osteopontin

The balance of myeloid populations and lymphoid populations must be well controlled. Scientists found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct effects in shifting this balance through cell-type-specific regulation of apoptosis. Intracellular OPN diminished the population size of myeloid progenitor cells and myeloid cells, and secreted OPN increased the population size of lymphoid cells. [Nat Immunol] Abstract

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Inhibition of the B7-H3 Immune Checkpoint Limits Tumor Growth by Enhancing Cytotoxic Lymphocyte Function

The authors analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8⁺ T cells. [Cell Res] Abstract

CTCF Orchestrates the Germinal Center Transcriptional Program and Prevents Premature Plasma Cell Differentiation

Researchers showed that the CCCTC-binding factor (CTCF) is required for the germinal centers (GC) reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional program, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of plasma cells differentiation. [Nat Commun] Full Article | Press Release

PD-L1 and IAPs Co-Operate to Protect Tumors from Cytotoxic Lymphocyte-Derived TNF

Investigators showed that CD8⁺ T cells and NK cells potently kill tumor cells in the presence of the smac-mimetic, birinapant. Enhanced cytotoxic lymphocyte (CL) killing occurred through TNF secretion upon tumor antigen recognition or NK-activating receptor ligation. The perforin/granzyme route to CL-mediated tumor cell killing was dispensable for the efficacy of birinapant, emphasizing the importance of the TNF-mediated apoptosis pathway. [Cell Death Differ] Abstract

A Fusion Receptor as a Safety Switch, Detection and Purification Biomarker for Adoptive Transferred T Cells

Scientists describe the development of a fusion receptor (FR806) generated by engineering a cryptic 806 epitope of human epidermal growth factor receptor (EGFR) into the N-terminus of the full-length human folate receptor-α. The expression of FR806 allowed transduced T-cells to be targeted with CH12, a monoclonal antibody recognizing the 806 epitope but not wild-type EGFR in healthy tissues. FR806 therefore constitutes a specific cell-surface marker for the elimination of transduced T-cells. [Mol Ther] Abstract

Lurbinectedin Reduces Tumor-Associated Macrophages and the Inflammatory Tumor Microenvironment in Preclinical Models

Researchers investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumor-bearing mice. Administration of lurbinectedin significantly and selectively decreased the number of circulating monocytes and, in tumor tissues, that of macrophages and vessels. [Br J Cancer] Full Article

Eicosapentaenoic Acid and 5-HEPE Enhance Macrophage-Mediated Treg Induction in Mice

The effects of eicosapentaenoic acid (EPA) on infiltrated immune cell populations in adipose tissue and underlying mechanisms remain to be elucidated. Investigators performed flow cytometry of stromal vascular fraction of epididymal adipose tissues from C57BL/6J and ob/ob mice fed normal chow mixed with or without 5% EPA. The numbers of hematopoietic cells, including Tregs, were higher in both C57BL/6J and ob/ob mice fed EPA diet compared with control diet. EPA enhanced the induction of Tregs in co-cultures of adipose tissue macrophages and naïve T cells. [Sci Rep] Full Article

Dexamethasone Induced Inhibition of Dectin-1 Activation of Antigen Presenting Cells Is Mediated via STAT-3 and NF-κB Signaling Pathways

Researchers showed that antigen-presenting cells generated in the presence of dexamethasone have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands. [Sci Rep] Full Article

Combining Dendritic Cells and B Cells for Presentation of Oxidized Tumor Antigens to CD8⁺ T Cells

Investigators examined the effect of oxidized whole-cell lysate (ox-L) versus soluble fraction freeze–thaw lysate (s-L) on bone marrow-derived dendritic cells and macrophages, and magnetic bead-isolated splenic B cells. The antigen-presenting cells were used individually, or in combination, to prime T cells. CD8⁺ T cells produced interferon-γ in response to both s-L and ox-L, but only proliferated in response to ox-L. [Clin Transl Immunology] Full Article

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Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

Scientists discuss how cell metabolism influences T cell anti-tumor activity, the metabolic qualities of highly-functional T cells, and strategies to modulate metabolism for improving the immune response to tumors. [Cell Metab] Abstract

Regulation of the Immune System by Laminins

The authors summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. The role of the laminins in autoimmune diseases and transplantation is discussed. [Trends Immunol] Abstract

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

Celgene Corporation Enters into Global Strategic Immuno-Oncology Collaboration with BeiGene to Advance PD-1 Inhibitor Program for Solid Tumor Cancers

Celgene Corporation and BeiGene, Ltd. entered into a strategic collaboration to develop and commercialize BeiGene’s investigational anti-programmed cell death protein 1 (PD-1) inhibitor, BGB-A317, for patients with solid tumor cancers in the United States, Europe, Japan and rest of world outside Asia. [Celgene] Press Release

Servier and Transgene Have Become Partners to Apply Viral Vectorization Technology to the Engineering of Allogenic CAR-T

Servier and Transgene announced the signature of a research agreement on the application of viral vectorization technology for the production of allogenic CAR-T cell therapies. The aim is to obtain more efficient products for patients. [Servier] Press Release

Multiple Myeloma Research Foundation (MMRF) Announces $15 Million Investment in Immunotherapy Initiative

The MMRF announced that it is investing $15 million over the next three years to launch its immunotherapy initiative. The Initiative is an effort to fund the many urgent needs and areas of potential in immunotherapy. [The Multiple Myeloma Research Foundation] Press Release

ViraCyte Awarded $3.75M from NIH and FDA to Advance T Cell Immunotherapies

ViraCyte, LLC. announced that it has been awarded $3.75M from National Institutes of Health (NIH) and the FDA to advance its T cell immunotherapies. [ViraCyte, LLC.] Press Release

Evotec Received Funding from IFB Hamburg to Identify Antibody-Mediated T-Cell Immunotherapies

Evotec AG announced that the company has been awarded a ‘Programm für Innovation’ grant for a period of two years from the IFB Hamburg, to identify and develop therapeutic antibodies directed against novel immune-checkpoints on T-cells to improve future cancer treatments. [Evotec AG] Press Release

First in Human Administration of UCART123 in Cellectis’ AML Phase I Clinical Trial at Weill Cornell Medicine, New York-Presbyterian Hospital

Cellectis announced the first administration in the Phase I clinical study in acute myeloid leukemia (AML) for its investigational product UCART123, one of the company’s wholly-controlled TALEN^® gene-edited product candidates. This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate targeting CD123 to be investigated in clinical trials. [Cellectis] Press Release

Trump Administration Chooses Georgia Physician to Lead US Public-Health Agency

Obstetrician and gynecologist Brenda Fitzgerald will direct the US Centers for Disease Control and Prevention, Secretary of Health and Human Services Tom Price announced. [Nature News] Editorial

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

NEW AACR-NCI-EORTC International Conference on Molecular Targets & Cancer Therapeutics
November 5-9, 2017
Boston, Massachusetts, United States

NEW 2017 National Cancer Research Institute (NCRI) Cancer Conference
November 5-8, 2017
Liverpool, United Kingdom

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NEW Postdoctoral Fellow – Immunology (Oxford University)

NEW Principal Senior Scientist – Human Disease Immune Profiling/Precision Immunology (Sanofi)

NEW Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden (MIMS))

Scientists/Senior Scientists – Unconventional T Cell Research (Immunocore)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Scientist – Immunogenomics (University of Oxford)

Scientist – Neuroinflammation (University Health Network)

Postdoctoral Fellow – Neuroimmunology (The University of Texas MD Anderson Cancer Center)

Immunologist – Brain Cancer (Columbia University)

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

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