Human Immunology News Volume 8.20 | May 26 2020

TOP STORY

Deciphering Human Macrophage Development at Single-Cell Resolution

Researchers isolated CD45⁺ hematopoietic cells from human embryos at Carnegie stages 11 to 23 and subjected them to transcriptomic profiling by single-cell RNA sequencing, followed by functional characterization of a population of CD45⁺CD34⁺CD44⁺ yolk sac-derived myeloid-biased progenitors by single-cell culture. [Nature] Abstract

(Ranked by impact factor of the journal)

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity

Investigators showed that clinically relevant antagonists used for treating autoimmune conditions could be converted into potent FcγR-independent agonists with remarkable anti-tumor activity by isotype switching to hIgG2. [Cancer Cell] Full Article | Graphical Abstract

Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis

Human heart tissues were collected from the surgically removed hearts of patients who had undergone heart transplantation. The authors identified 26 cell subtypes among 34,665 cells. [Circulation] Abstract

Human CD83-Targeted Chimeric Antigen Receptor T Cells Prevent and Treat Graft-versus-Host Disease

Human CD83 CAR T cells eradicated pathogenic CD83⁺ target cells, significantly increased the ratio of regulatory T cells to allo-activated conventional CD4⁺ T cells, and provided durable prevention of xenogeneic graft versus host disease (GVHD). CD83 CAR T cells were also capable of treating xenogeneic GVHD. [J Clin Invest] Abstract | Full Article | Graphical Abstract

A Micropeptide Encoded by lncRNA MIR155HG Suppresses Autoimmune Inflammation via Modulating Antigen Presentation

Scientists report that human lncRNA MIR155HG encodes a 17-amino acid micropeptide, which they termed miPEP155 (P155). MIR155HG was highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacted with the adenosine 5′-triphosphate binding domain of heat shock cognate protein 70, a chaperone required for antigen trafficking and presentation in dendritic cells. [Sci Adv] Full Article

Cytokine IL-36γ Improves CAR T-Cell Functionality and Induces Endogenous Antitumor Response

The authors demonstrated that CAR T cells secreting a cytokine interleukin-36γ showed significantly improved CAR T-cell expansion and persistence, and resulted in superior tumor eradication compared with conventional CAR T cells. [Leukemia] Abstract

Inhibition of Ubiquitin-Specific Protease 7 Sensitizes Acute Myeloid Leukemia to Chemotherapy

Investigators demonstrated that inhibition of deubiquitinylase USP7 significantly reduced cell proliferation in vitro and in vivo, blocked DNA replication progression and increased cell death in acute myeloid leukemia. [Leukemia] Full Article

The FBW7-MCL-1 Axis Is Key in M1 and M2 Macrophage-Related Colon Cancer Cell Progression: Validating the Immunotherapeutic Value of Targeting PI3Kγ

Scientists addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 colorectal cancer cell patient tissue samples and investigated the mechanisms underlying TAM-related colon cancer progression with respect to PI3Kγ regulation using in vitro, in vivo, and ex vivo approaches. [Exp Mol Med] Full Article

Oncolytic Activity of Targeted Picornaviruses Formulated as Synthetic Infectious RNA

A new infectious RNA retained high specific infectivity, rapidly generating replicating microRNA-detargeted viruses following transfection in H1-HeLa cells. In contrast to alternatively configured iRNAs that were tested in parallel, intratumoral administration of R-CVA21 generated a spreading oncolytic infection that was curative in treated animals without associated myotoxicity. [Mol Ther Oncolytics] Abstract | Full Article | Graphical Abstract

Sphingomyelin Synthase 2 Facilitates M2-Like Macrophage Polarization and Tumor Progression in a Mouse Model of Triple-Negative Breast Cancer

Researchers investigated whether sphingomyelin synthase 2 (SMS2) inhibitor or SMS2 gene knockout could reduce macrophages M2 polarization and tumor progression in a mouse model of triple negative breast cancer (TNBC). They showed that SMS2 mRNA expression was linked to immunosuppressive tumor microenvironment and poor prognosis in TNBC patients. [Acta Pharm] Abstract

The T Cell Differentiation Landscape Is Shaped by Tumour Mutations in Lung Cancer

How the tumor microenvironment affects CD4 and CD8 T cell differentiation in untreated tumors and whether this affects patient outcomes is unknown. Researchers paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated non-smell cell lung cancer to examine these relationships. [Nat Cancer] Abstract

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Host–Microbiota Interactions in Immune-Mediated Diseases

Investigators discuss the mechanisms of how the microbiota contributes to the predisposition, initiation and perpetuation of immune-mediated diseases in the context of a genetically prone host. [Nat Rev Microbiol] Abstract

Transcriptional Control of Mature B Cell Fates

The authors summarize emerging data on the role of transcription factors- particularly the ETS and IRF families- in regulating marginal zone B and follicular B lineage selection. [Trends Immunol] Abstract

Chimeric Antigen Receptor Signaling: Functional Consequences and Design Implications

Chimeric antigen receptor (CAR) T cell therapy has transformed the care of refractory B cell malignancies and holds tremendous promise for many aggressive tumors. Despite overwhelming scientific, clinical, and public interest in this rapidly expanding field, fundamental inquiries into CAR T cell mechanistic functioning are still in their infancy. [Sci Adv] Full Article

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

Kleo Pharmaceuticals and Celularity Enter into Research Collaboration to Rapidly Develop Allogeneic NK Cell Combination Therapies for COVID-19 and Multiple Myeloma

Kleo Pharmaceuticals, Inc. and Celularity, Inc. announced a pre-clinical research collaboration to rapidly advance synergistic combinations of each company’s technology platform as potential treatments for COVID-19 and multiple myeloma. [Kleo Pharmaceuticals, Inc.] Press Release

Alethia Biotherapeutics Announces Receipt of FDA Authorization to Begin Phase II Development for its EMT Inhibitor, AB-16B5

Alethia Biotherapeutics announced that the FDA has cleared its Phase II Investigational new drug application for AB-16B5, a potent inhibitor of the epithelial to mesenchymal transition. [Alethia Biotherapeutics] Press Release

Kitov Announces US FDA Acceptance of Investigational New Drug Application to Conduct Phase I/II Clinical Trial of NT219 in Multiple Types of Advanced Cancer Patients

Kitov Pharma Ltd. announced that the FDA has accepted its Investigational New Drug application to conduct a Phase I/II clinical trial of NT219, a novel agent addressing treatment resistance in advanced cancer. [Kitov Pharma Ltd.] Press Release

US Lawmakers Unveil Bold $100 Billion Plan to Remake NSF

The National Science Foundation (NSF) would get a sweeping remake-including a new name, a huge infusion of cash, and responsibility for maintaining US global leadership in innovation-under bipartisan bills that have been introduced in both houses of Congress. [ScienceInsider] Editorial

They Redesigned PubMed, a Beloved Website. It Hasn’t Gone Over Well

Unfortunately for PubMed’s caretakers, a sweeping redesign unveiled this week has left many PubMed users fuming-and airing their sometimes curse-laden complaints on social media. [ScienceInsider] Editorial

Will Trump White House Tear Down Journal Paywalls? Many Anxiously Await a Decision

Scientific publishers, universities, librarians, and open-access advocates are waiting anxiously to see whether the Trump administration will end a long-standing policy and require that every scholarly article produced with US funding be made immediately free to all. [ScienceInsider] Editorial

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NEW Postdoctoral Researchers – Tumor Immunology (Universitätsklinikum Carl Gustav Carus Dresden)

NEW Postdoctoral Fellow – Glycobiology and Immunology (Brigham and Women’s Hospital)

NEW Research Associate – Immunology Assays (Sanofi)

Postdoctoral Fellow – Immune Regulation in Gastrointestinal Cancers (City of Hope)

Research Assistant – Cellular and Humoral Immune Response (Caprion)

Postdoctoral Researcher – Oncolytic Virus (ViraTherapeutics GmbH)

Postdoctoral Researcher – DNA Break Repair and Recombination (Fred Hutchinson Cancer Research Center)

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

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

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

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