Human Immunology News Volume 8.15 | Apr 21 2020

TOP STORY

Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies

The authors developed a widely adaptable technology to barcode and track targeted integrations of large non-viral DNA templates and applied it to perform pooled knockin screens in primary human T cells. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Interleukin 17 and Senescent Cells Regulate the Foreign Body Response to Synthetic Material Implants in Mice and Humans

To explore the immune and stromal connections underpinning the foreign body response, researchers analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. They found increased numbers of IL17-producing γδ⁺ T cells and CD4⁺ T helper 17 cells as well as senescent stromal cells in the fibrotic capsules. [Sci Transl Med] Abstract

Synthesis and Evaluation of Designed PKC Modulators for Enhanced Cancer Immunotherapy

Investigators report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, they synthesized a series of bryostatin analogs designed to maintain affinity for bryostatin’s target protein kinase C (PKC) while enabling exploration of their divergent biological functions. [Nat Commun] Full Article

Starvation and Antimetabolic Therapy Promote Cytokine Release and Recruitment of Immune Cells

The authors analyzed secretomes from glucose-deprived cells, which revealed up-regulation of multiple cytokines and chemokines, including IL-6 and IL-8, in response to starvation stress. Starvation-induced cytokines were cell type-dependent, and they were also released from primary epithelial cells. [Proc Natl Acad Sci USA] Full Article

The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan

Researchers hypothesized that the Set7 methyltransferase has an important role in trained immunity induced by β-glucan. Using pharmacological studies of human primary monocytes, they identified trained immunity-specific immunometabolic pathways regulated by Set7, including a previously unreported H3K4me1-dependent plasticity in the induction of oxidative phosphorylation. [Cell Rep] Full Article | Graphical Abstract

Tumor-Associated Macrophages Promote Ovarian Cancer Cell Migration by Secreting Transforming Growth Factor Beta Induced (TGFBI) and Tenascin C

Investigators observed that high-grade serous ovarian carcinoma migration was promoted by soluble mediators from ascites-derived tumor associated microphages (TAM), which could be emulated by conditioned medium from monocyte-derived macrophages (MDM) differentiated in ascites to TAM-like MDM by ascites. [Cell Death Dis] Full Article

Human Regulatory T Cells from Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

Scientists compared the phenotypic profiles of human T regulatory cells (Tregs) isolated from cord blood versus the more traditional source, adult peripheral blood. They conducted analysis of fresh and ex vivo expanded Treg subsets at both the single cell and bulk levels. [Front Immunol] Full Article

Development of a Unique T-Cell Receptor Gene-Transferred Tax-Redirected T-Cell Immunotherapy for Adult T-Cell Leukemia

T-cell receptor-ɑ/β genes were cloned from a previously established cytotoxic T-cell clone and transduced into peripheral blood mononuclear cells of healthy volunteers using a retroviral siTCR vector. Investigators assessed the cytotoxic efficacy against human T cell lymphotropic virus type-1-infected T-cells or primary adult T-cell leukemia/lymphom cells both in vitro and in vivo. [Biol Blood Marrow Transplant] Abstract

Cigarette Smoking Induces Human CCR6⁺T h17 Lymphocytes Senescence and VEGF-A Secretion

Researchers evaluated the sensitivity of CD4⁺ Th17 lymphocytes to cigarette smoke-induced senescence. Mucosa-homing CCR6⁺ Th17- were compared to CCR6_neg -and regulatory T peripheral lymphocytes after exposure to cigarette smoke extract. [Sci Rep] Full Article

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Dissecting the Biology of Allogeneic HSCT to Enhance the GvT Effect whilst Minimizing GvHD

The authors review learnings from preclinical modelling and clinical studies relating to the graft-versus-tumor (GvT) effect, focusing on mechanisms of relapse and on immunomodulatory strategies that are being developed to overcome disease recurrence after both allogeneic haematopoietic stem cell transplantation (HSCT) and autologous HSCT. [Nat Rev Clin Oncol] Abstract | Full Article

The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation

Inflammation is closely related with the progression of cancer and is an indispensable component that orchestrates the tumor microenvironment. Studies suggest that different mediator and cellular effectors, including cytokines, chemokines as well as some transcription factors play a crucial role during cancer-related inflammation. [Mol Ther Nucleic Acids] Abstract

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

Mogrify and Sangamo Announce Collaboration and Exclusive License Agreement for Mogrify’s iPSC- and ESC-Derived Regulatory T Cells

Mogrify Ltd and Sangamo Therapeutics announced that they have executed a collaboration and exclusive license agreement for Sangamo to develop allogeneic cell therapies from Mogrify’s proprietary induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) and Sangamo’s zinc finger protein gene-engineered chimeric antigen receptor regulatory T cell technology. [Mogrify Ltd] Press Release

WindMIL Therapeutics Opens Combination Therapy Portion of Its Phase IIa Clinical Trial of Marrow-Infiltrating Lymphocytes (MILs™) for Treatment of Patients with Non-Small Cell Lung Cancer

WindMIL Therapeutics announced it has begun enrollment in the combination therapy portion of its open-label, multi-center Phase IIa clinical trial to assess the safety and efficacy of MILs in patients with locally advanced unresectable or metastatic non-small cell lung cancer who are refractory to, or have relapsed on, an anti-PD-1-containing regimen. [WindMIL Therapeutics (GlobeNewswire, Inc.)] Press Release

Untapped Potential: More US Labs Could Be Providing Tests for Coronavirus

A survey of more than 4,000 researchers in the United States suggests that better coordination at an institutional and national level could make hundreds of thousands more tests for coronavirus available. [Nature News] Editorial

How Research Funders Are Tackling Coronavirus Disruption

While science is crucial to the fight against COVID-19, researchers confined to their homes and unable to carry on with grant-funded work are becoming increasingly concerned about how the coronavirus pandemic will affect their funding. [Nature News] Editorial

Ending Coronavirus Lockdowns Will Be a Dangerous Process of Trial and Error

After the novel coronavirus made its way from China around the world, one country after another adopted harsh measures to stop SARS-CoV-2 from spreading and overwhelming hospitals. They have hit the pause button on their economies and their citizens’ lives, stopping sports events, religious services, and other social gatherings. [ScienceInsider] Editorial

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NEW Postdoctoral Researcher – Ion Channels in Immunolgoy (New York Univeristy)

Scientist – Post-Injury Inflammation (Athersys, Inc.)

Senior Scientist – Oncology Biomarker Development (Genentech, Inc.)

Associate Professor – Cancer Biology (University of Cincinnati)

Scientist – Cancer Immunology and Immunotherapy (Genentech, Inc.)

Co-Director – Anti-Cancer Immune Response (Rutgers Cancer Institute of New Jersey)

Research Fellow – Mucosal Immunology (University of Michigan)

Faculty Member – Neuro-Oncology (Wake Forest School of Medicine)

Postoctoral Scientist – Molecular and Cellular Immunology (Technical University of Munich)

Postdoctoral Researcher – Adoptive T-Cell Therapies (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Moffitt Cancer Center and Research Institute)

Postdoctoral Researchers – B Lymphocyte Regulation (NIH National Institute on Aging)

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