Human Immunology News Volume 6.07 | Feb 20 2018

TOP STORY

TGFβ Attenuates Tumor Response to PD-L1 Blockade by Contributing to Exclusion of T Cells

Researchers examined tumors from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent and identified major determinants of clinical outcome. Response to treatment was associated with CD8⁺ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumor mutation burden. [Nature] Abstract

(Ranked by impact factor of the journal)

Circulating T_FH Cells, Serological Memory, and Tissue Compartmentalization Shape Human Influenza-Specific B Cell Immunity

Using recombinant hemagglutinin probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, scientists showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5⁻CXCR3⁺ antibody-secreting B cell population, CD21^hiCD27⁺ memory B cells, and CD21^loCD27⁺ B cells. [Sci Transl Med] Abstract

Microenvironmental Regulation of the IL-23R/IL-23 Axis Overrides Chronic Lymphocytic Leukemia Indolence

Researchers investigated the interleukin-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage chronic lymphocytic leukemia patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rβ1 chain. [Sci Transl Med] Abstract

PSTPIP1 Controls Immune Synapse Stability in Human T-Cells

From genetic screening of primary immunodeficiency patients, the authors identified two mutations in PSTPIP1, R228C and T274M which they further characterized in primary patient T-cells. [J Allergy Clin Immunol] Abstract

Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

Investigators identified hypermethylated in cancer 1 (HIC1) as a transcription factor upregulated early during the differentiation of human in vitro induced Treg cells. [Cell Rep] Full Article | Graphical Abstract

Optimizing EphA2-CAR T Cells for the Adoptive Immunotherapy of Glioma

Researchers demonstrated that T cells expressing CD28.ζ and 41BB.ζ chimeric antigen receptors with short spacers had similar effector function, resulting in potent antitumor activity. [Mol Ther Methods Clin Dev] Full Article

Glucocorticoids Promote Apoptosis of Proinflammatory Monocytes by Inhibiting ERK Activity

Scientists report that the glucocorticoid, dexamethasone, induces apoptosis in granulocyte macrophage-colony stimulating factor (CSF)-treated human monocytes while having no impact on macrophage-CSF-induced monocyte survival. [Cell Death Dis] Full Article

Human Neutrophils Can Mimic Myeloid-Derived Suppressor Cells (PMN-MDSC) and Suppress Microbead or Lectin-Induced T Cell Proliferation through Artefactual Mechanisms

The authors report that human conventional CD15⁺ neutrophils can be isolated in the peripheral blood mononuclear cell layer during Ficoll gradient separation, and that they can impair T cell proliferation in vitro without concomitant neutrophil activation and killing. [Sci Rep] Full Article

FOXP3 Renders Activated Human Regulatory T Cells Resistant to Restimulation-Induced Cell Death by Suppressing SAP Expression

Scientists demonstrated that normal regulatory T cells expressed very low levels of SLAM-associated protein (SAP) compared to conventional T cells. Forkhead box P3 (FOXP3) reduces SAP expression by directly binding to and repressing the SH2D1A promoter. [Cell Immunol] Abstract

Human Vδ3⁺ γδ T Cells Induce Maturation and IgM Secretion by B Cells

Researchers investigated if Vδ3 T cells can promote B cell differentiation, antibody secretion and cytokine production in vitro. Vδ3 T cells were sorted from healthy human blood and expanded using phytohemagglutinin and cultured with freshly isolated human B cells. [Immunol Lett] Abstract

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Human T Cell Development, Localization, and Function throughout Life

Scientists discuss how human T cells develop and provide essential immune protection at different life stages and highlight tissue localization and subset delineation as key determinants of the T cell functional role in immune responses. [Immunity] Abstract

A New Classification System for IgG4 Autoantibodies

The author establishes a modified classification system based on Witebsky’s postulates to determine IgG4 pathogenicity in IgG4 autoimmune diseases, reviews characteristics and pathogenic mechanisms of IgG4 in these disorders, and also investigates the contribution of other antibody entities to pathophysiology by additional mechanisms. [Front Immunol] Full Article

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

Obsidian Therapeutics to Present Data Demonstrating Regulation of Protein Activity with Its Next-Generation CAR-T Platform

Obsidian Therapeutics, Inc. announced the presentation of preclinical data on its technology platform and applications. [Press release from Obsidian Therapeutics, Inc. (Business Wire Inc.) discussing research presented at the 2018 Keystone Symposium on Emerging Cellular Therapies: T Cells and Beyond, Keystone] Press Release

Poseida Therapeutics Presents Stem Cell Memory CAR-T Therapy for Prostate Cancer

Poseida Therapeutics Inc. presented preclinical data on P-PSMA-101. P-PSMA-101 is the company’s PSMA-specific stem cell memory CAR-T drug candidate for the treatment of prostate cancer, which is the most common cancer among men in the United States. [Press release from Poseida Therapeutics Inc. discussing research presented at the 2018 Keystone Symposium on Emerging Cellular Therapies: T Cells and Beyond, Keystone] Press Release

Sangamo Presents Oncology Genome Editing Capabilities

Sangamo Therapeutics presented preclinical data demonstrating the company’s engineering capabilities in T cell genome editing using zinc finger nucleases. Sangamo Scientist Sumiti Jain, Ph.D. delivered the presentation, “Dual Knock-Out of Endogenous T-Cell Receptor and Human Leukocyte Antigen and Site-Specific Insertion of a CD19-CAR: Implications for Allogeneic T Cell Therapy”. [Press release from Sangamo Therapeutics, Inc. discussing research presented at the 2018 Keystone Symposium on Emerging Cellular Therapies: T Cells and Beyond, Keystone] Press Release

Fate Therapeutics Announces First Subject Treated with FATE-NK100 in DIMENSION Study for Advanced Solid Tumors

Fate Therapeutics, Inc. announced that the first subject has been treated in the DIMENSION study of FATE-NK100 for the treatment of advanced solid tumors. [Fate Therapeutics, Inc.] Press Release

Celgene Unveils State-of-the-Art Cellular Immunotherapy Manufacturing Facility

Celgene completed the first phase of a renovation at its Summit West campus that will house a state-of-the-art cellular immunotherapy manufacturing center. The 135,000 square-foot facility will enable the company to expand investigational programs and eventually the potential commercial launch related to bb2121, its chimeric antigen receptor (CAR T) therapy being developed for certain multiple myeloma patients in conjunction with its partner bluebird bio. [Celgene] Press Release

Indonesian Scientists Hamstrung by Year-Long Funding Delay

Indonesian scientists expecting to receive hundreds of thousands of dollars for research are stuck in limbo because the country’s first dedicated science-funding agency is struggling to raise enough money. [Nature News] Editorial

Italian Election Leaves Science out in the Cold

As campaigning ahead of Italy’s national election enters its final weeks, researchers in the country fear that budget cuts and declining interest in science will only continue — whatever the outcome of the vote. [Nature News] Editorial

Biden Blasts Science Denialists, Calls to Dramatically Speed Up Fight against Cancer

Fresh off a plane from the NATO meeting in Munich, where he’d conferred with world leaders on global defense, former U.S. Vice President Joe Biden issued a forceful call here last night to build on the “Cancer Moonshot” he started while in the White House and transform the way the world fights cancer. [ScienceInsider] Editorial

NEW Aegean Conferences: 7^th International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems
June 3-8, 2018
Crete, Greece

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

NEW Principal Scientist – Immunosciences Drug Discovery (Bristol-Myers Squibb)

NEW Postdoctoral Fellow – T-Cell Therapy (Memorial Sloan Kettering Cancer Center)

NEW PhD Studentship – Treg Cell Research (Universitätsklinikum Carl-Gustav-Carus Dresden)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Scientist Opportunities – Biomedical Research (Cedars-Sinai)

Senior Director – Immuno-Oncology Research (Alector LLC)

Research Scientist – Oncology Research (MedImmune)

Postdoctoral Researcher – Cellular and Molecular Immunology (Karolinska Institutet)

Postdoctoral Fellow – Immunology/Vascular/Stromal Biology (Hospital for Special Surgery and Weill Cornell Medicine)

Postdoctoral Position – Microbiology and Immunology (University of Maryland)

Head of Laboratory – Cancer Vaccines/Oncolytic Viruses (Boehringer Ingelheim)

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