Human Immunology News Volume 5.47 | Nov 28 2017

TOP STORY

Second ‘Don’t Eat Me’ Signal Found on Cancer Cells

CD47 is an important inhibitor of cancer-killing immune cells called macrophages. Now Stanford researchers have identified another, similar way to activate macrophages to destroy cancer cells. [Press release from Stanford Medicine discussing online prepublication in Nature Immunology] Press Release | Abstract

(Ranked by impact factor of the journal)

Single-Cell Analysis Reveals the Continuum of Human Lympho-Myeloid Progenitor Cells

Scientists demonstrated that lympho-myeloid progenitor populations in cord blood — lymphoid-primed multi-potential progenitors, granulocyte-macrophage progenitors and multi-lymphoid progenitors — were functionally and transcriptionally distinct and heterogeneous at the clonal level, with progenitors of many different functional potentials present. [Nat Immunol] Abstract

Mutational and Putative Neoantigen Load Predict Clinical Benefit of Adoptive T Cell Therapy in Melanoma

Researchers searched for predictive biomarkers to adoptive T-cell therapy in melanoma. They report that clinical benefit was associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load were significantly associated with improved progression-free and overall survival. [Nat Commun] Full Article | Press Release

Critical Role of the HDAC6–Cortactin Axis in Human Megakaryocyte Maturation Leading to a Proplatelet-Formation Defect

The authors showed that histone deacetylase (HDAC)6 inhibition and genetic knockdown lead to a strong decrease in human proplatelet formation (PPF). Unexpectedly, HDAC6 inhibition-induced tubulin hyperacetylation had no effect on PPF. [Nat Commun] Full Article

MiR-29b Antagonizes the Pro-Inflammatory Tumor-Promoting Activity of Multiple Myeloma-Educated Dendritic Cells

Investigators hypothesized that multiple myeloma cells might recruit and reprogram dendritic cells (DCs) to a tumor-permissive phenotype by changes within their miRNA network. By analyzing six different miRNA-profiling datasets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor associated DCs. [Leukemia] Full Article

Anti-SIRPα Antibody Immunotherapy Enhances Neutrophil and Macrophage Antitumor Activity

Researchers developed the monoclonal antibody KWAR23, which binds human inhibitory receptor signal regulatory protein-α (SIRPα) with high affinity and disrupts its binding to CD47. Administered by itself, KWAR23 was inert, but given in combination with tumor-opsonizing monoclonal antibodies, KWAR23 greatly augmented myeloid cell-dependent killing of a collection of hematopoietic and nonhematopoietic human tumor-derived cell lines. [Proc Natl Acad Sci USA] Abstract | Press Release

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

The number of group 2 innate lymphoid cells (ILC2) is increased in patients with asthma, and the authors investigated how testosterone attenuates ILC2 function. In patients with moderate to severe asthma, they determined that women have an increased number of circulating ILC2 compared to men. [Cell Rep] Full Article | Press Release | Graphical Abstract

Generation of “Off-the-Shelf” Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells

To provide unlimited “off-the-shelf” natural killer (NK) cells that serve many recipients, investigators designed and demonstrated a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent stem cells. [Stem Cell Reports] Full Article

Engineering Protein-Secreting Plasma Cells by Homology-Directed Repair in Primary Human B Cells

The authors developed methods for efficient genome editing of primary B cells isolated from peripheral blood. By delivering CRISPR/Cas9 ribonucleoprotein complexes under conditions of rapid B cell expansion, they achieved site-specific gene disruption at multiple loci in primary human B cells. They showed that introduction of B-cell activating factor into plasma cells promotes their engraftment into immunodeficient mice. [Mol Ther] Full Article | Graphical Abstract

Ly6G⁺ Neutrophil-Derived miR-223 Inhibits the NLRP3 Inflammasome in Mitochondrial DAMP-Induced Acute Lung Injury

Researchers demonstrated that miR-223 limits the number of Ly6G⁺ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate acute lung injury induced by mitochondrial damage-associated molecular patterns. miR-223 blocked bone marrow-derived Ly6G⁺ neutrophil differentiation and inhibited peripheral cytokine release. [Cell Death Dis] Full Article

The Generation of Human γδT Cell-Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture

Occasionally, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T-cell exhaustion, the authors generated induced pluripotent stem cells that harbor the same T-cell receptor genes as their original T-cells, which provide nearly limitless sources for antigen-specific cytotoxic T lymphocytes. [Stem Cells Transl Med] Full Article

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The Broad Spectrum of Human Natural Killer Cell Diversity

The authors review the current understanding of the breadth and generation of human natural killer cell diversity. [Immunity] Abstract

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

TapImmune to Present at World Vaccine & Immunotherapy Congress West Coast

TapImmune Inc. announced its Chairman and Strategic Advisor Glynn Wilson, Ph.D., and Senior Director of Molecular Biology & Virology Robert Florkiewicz, Ph.D., will give an oral presentation titled, “Increasing the potency of DNA-based immunotherapies using PolyStart^™ peptide expression system.” [Press release from TapImmune Inc. discussing research to be presented at the 2017 World Vaccine & Immunotherapy Congress West Coast, San Diego] Press Release

Biocept and UC San Diego Medical Center Announce Clinical Study Collaboration to Demonstrate Utility of Biocept’s Liquid Biopsy Test in Immunotherapy

Biocept, Inc. announced entering into a clinical study agreement with the University of California, San Diego (UCSD) Medical Center. Led by recognized immune-oncology and precision medicine specialist Sandip Patel, M.D., Assistant Professor at UCSD School of Medicine, the 100-patient study is designed to clinically validate Biocept’s Target Selector^™ PD-L1 assay for patients diagnosed with non-small cell lung cancer. [Biocept, Inc.] Press Release

Prometic Reports Positive Interim Clinical Data from Ongoing Intravenous Immunoglobulin (IVIG) Pivotal Phase III Trial

Prometic Life Sciences Inc. announced positive interim six-month clinical data from its ongoing pivotal IVIG Phase III clinical trial in patients suffering from primary immunodeficiencies following review of the data by the Data Safety Monitoring Board, which confirmed no significant safety issues and that efficacy appeared to be comparable to existing commercial IVIG products. [Prometic Life Sciences Inc.] Press Release

Regen BioPharma, Inc. Begins In Vivo Assessment of Small Molecule Agonists to NR2F6 Nuclear Receptor

Regen BioPharma Inc. initiated in vivo and ex vivo assessments to determine the effects of some of the company’s NR2F6 small molecule agonists in live rats and in tissues derived from humans and rats. Key attributes that are being measured include pH, plasma and liver microsomal stability, along with pharmacokinetics. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

15 Faculty Members Elected as AAAS Fellows

Fifteen Vanderbilt University faculty members conducting a range of biomedical and clinical research have been elected fellows of the American Association for the Advancement of Science (AAAS) this year. [Vanderbilt University] Press Release

Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

Eager to speed development of revolutionary treatments, the Food and Drug Administration recently announced that it would expedite approval of experimental gene therapies. But the regulatory process may not be the biggest obstacle. [The New York Times] Editorial

United Kingdom Relies on Science to Revive Flagging Economy

The United Kingdom has laid out how it will pour money into research to boost its economy — including cash for artificial intelligence and other high-tech industries — as the country prepares to leave the European Union in 2019. [Nature News] Editorial

Zimbabwe’s Researchers Hope Political Change Will Revitalize Science

Academics are optimistic that the end of Robert Mugabe’s authoritarian rule could boost research and international collaboration. [Nature News] Editorial

NEW Gordon Research Conferences: Plasminogen Activation and Extracellular Proteolysis
February 11-16, 2018
Ventura, California, United States

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NEW Postdoctoral Positions – Immunotherapy (University of Houston)

NEW PhD Candidate – Innate Immunity in Lung Adenocarcinoma (Helmholtz Zentrum München)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Positions – Cytokines in Immunity, Stem Cells and Tissue Repair (Weill Cornell Medicine)

Postdoctoral Position – Immunology (Ghent University)

Postdoctoral Scientist – Molecular Genetics of Human T Cell Development (Ghent University)

Postdoctoral Fellow – Mucosal Immunology (University of Lorraine)

Postdoctoral Fellow – Mucosal Infections (University of Utah)

Postdoctoral Positions – Rare Immune Disorders (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Tenured Track Faculty – Regenerative and Immune Engineering (Johns Hopkins University Biomedical Engineering)

Scientist – Immune Oncology (Dana-Farber Cancer Institute)

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