Human Immunology News Volume 8.21 | June 2 2020

TOP STORY

Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy

In treatment-naive high-grade serous ovarian cancer, researchers found that immune-cell-excluded and inflammatory microenvironments co-existed within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

Lineage-Dependent Gene Expression Programs Influence the Immune Landscape of Colorectal Cancer

Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. [Nat Genet] Abstract

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma

Investigators report three immunotherapeutic modalities based on a human anti-CD133 antibody fragment that targeted a unique epitope present in glycosylated and non-glycosylated CD133 and studied their effects on targeting CD133⁺ cells in patient-derived models of glioblastoma. [Cell Stem Cell] Abstract | Graphical Abstract

Identification of Two DNA Methylation Subtypes of Waldenström’s Macroglobulinemia with Plasma and Memory B Cell Features

The authors integrated genome-wide DNA methylation, transcriptome, mutation and other phenotypic features of tumor cells from 35 MYD88-mutated Waldenström’s macroglobulinemia patients in relation to normal plasma and B cell subsets. [Blood] Abstract

The Tumor Microenvironment Shapes Dendritic Cell Plasticity in a Human Organotypic Melanoma Culture

By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, researchers generated a reconstructed tumor microenvironment that closely resembled tumor growth as observed in human lesions and supported cell survival and function. [Nat Commun] Full Article

Single Cell Transcriptomics Reveals Opioid Usage Evokes Widespread Suppression of Antiviral Gene Program

The authors performed single-cell RNA sequencing of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evoked widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. [Nat Commun] Full Article

Y-RNA Subtype Ratios in Plasma Extracellular Vesicles Are Cell Type- Specific and Are Candidate Biomarkers for Inflammatory Diseases

Researchers investigated which macromolecular structures in plasma contained full length Y-RNA and whether the levels of three Y-RNA subtypes in plasma changed during systemic inflammation. [J Extracell Vesicles] Full Article

Anti-RhD Antibody Therapy Modulates Human Natural Killer Cell Function

Investigators showed that anti-RhD antibodies induced human NK cell degranulation. Mechanistically, they demonstrated that NK cell degranulation was mediated by binding of the Fc segment of anti-RhD antibodies to CD16, the main Fcγ receptor expressed on NK cells. [Haematologica] Abstract

Amplification of Transglutaminase 2 Enhances Tumor-Promoting Inflammation in Gastric Cancers

Scientists investigated a novel role for transglutaminase 2 in the development of tumor-promoting inflammation and recruitment of tumor-associated macrophages to gastric cancer tissues. [Exp Mol Med] Full Article

Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer

Lentiviral vectors were used to express the extracellular domain of human PD-1 or the scFv region of αPD-L1 that bind to PD-L1, and each was fused to intracellular signaling domains containing CD3 zeta, CD28, and 4-1BB. [Mol Ther Oncolytics] Abstract | Full Article | Graphical Abstract

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Signaling from T Cell Receptors (TCRs) and Chimeric Antigen Receptors (CARs) on T Cells

The authors systematically review the knowns and unknowns of TCR and CAR signaling, from the contact of receptors and antigens, proximal signaling, immunological synapse formation, and late signaling outcomes. [Cell Mol Immunol] Abstract

Maternal and Fetal T Cells in Term Pregnancy and Pre-Term Labor

Investigators describe the established and proposed roles for maternal T cells at the maternal–fetal interface in normal term parturition, as well as the demonstrated contributions of such cells to the pathological process of pre-term labor and birth. [Cell Mol Immunol] Abstract

Revisiting the Role of CD4⁺ T Cells in Cancer Immunotherapy-New Insights into Old Paradigms

Scientists give an overview of the multifaceted role of CD4⁺ T cells in the anti-tumor immune response, with an emphasis on recent evidence that CD4⁺ T cells play a bigger role than previously thought. [Cancer Gene Ther] Full Article

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Achilles Therapeutics Doses First Patient in Phase I/II Study in Recurrent or Metastatic Malignant Melanoma

Achilles Therapeutics announced that it has dosed the first patient in a Phase I/II study of a clonal neoantigen T cell therapy in patients with recurrent or metastatic malignant melanoma. [Achilles Therapeutics] Press Release

Junior Researchers Hit by Coronavirus-Triggered Hiring Freezes

Juan Manuel Vazquez thought he knew where his career would take him after he wrapped up his PhD in genetics at the University of Chicago in Illinois in May. But the COVID-19 pandemic threatened to upend his plans. [Nature News] Editorial

Sputnik Moment or Budget Breaker: How Will the Pandemic Alter Research Funding?

As the pandemic’s economic toll grows around the world, some experts fear it could harm science for decades by putting many thousands of researchers out of work and forcing nations to slash funding as they rebuild societies. [Nature News] Editorial

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NEW Technician – Cell Screening and Assay Development (AbCellera Biologics, Inc.)

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

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

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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