Human Immunology News Volume 8.22 | Jun 9 2020

TOP STORY

Multi-Phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies

Scientists delineated four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells they measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

A Minority of T Cells Recognizing Tumor-Associated Antigens Presented in Self-HLA Can Provoke Anti-Tumor Reactivity

The authors investigated whether T cells with sufficient avidity to recognize naturally overexpressed self-antigens in the context of self-HLA could be found in the T-cell repertoire of healthy donors. [Blood] Abstract

Intratumoral γδ T-cell Infiltrates, CCL4/5 Protein Expression and Survival in Patients with Hepatocellular Carcinoma

Scienitsts quantified the amount of γδ T-cells using a γδ T-cell-specific gene signature in 247 Chinese hepatocellular carcinoma (HCC) patients. They also validated the γδ T-cell signature in American HCC patients. [Hepatology] Abstract

B7-H3 Immune Checkpoint Expression Is a Poor Prognostic Factor in Colorectal Carcinoma

B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. [Mod Pathol] Abstract

Novel XIAP Mutation Causing Enhanced Spontaneous Apoptosis and Disturbed NOD2 Signalling in a Patient with Atypical Adult-Onset Crohn’s Disease

Researchers present a novel XIAP mutation identified in a patient with atypical adult-onset inflammatory bowel disease complicated by relapsing haemophagocytic lymphohistiocytosis, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene created a premature stop codon, and caused a severe reduction in XIAP protein expression. [Cell Death Dis] Full Article

The Relationships between Systemic Cytokine Profiles and Inflammatory Markers in Colorectal Cancer and the Prognostic Significance of These Parameters

Interleukin (IL)-1β, IL-6, IL-8, IL-9, IL-10, tumor necrosis factor-α and vascular endothelial growth factor serum levels were measured using multiplex bead assays in colorectal cancer patients. [Br J Cancer] Abstract

Comprehensive Analysis of the PD-L1 and Immune Infiltrates of m⁶A RNA Methylation Regulators in Head and Neck Squamous Cell Carcinoma

Investigators systematically explored the correlations of prominent N6-methyladenosine (m⁶A) regulators with PD-L1 and immune infiltrates in 769 head and neck squamous cell carcinomas. The PD-L1 expression evidently associated with m⁶A regulators. [Mol Ther Nucleic Acids] Abstract | Full Article | Grapical Abstract

Cell Composition and Expansion Strategy Can Reduce the Beneficial Effect of AKT-Inhibition on Functionality of CD8⁺ T Cells

Researchers investigated the effect of AKT-inhibition on CD4⁺ T cells, during separate as well as total T cell expansions. Ex vivo AKT-inhibition preserved the early memory phenotype of CD4⁺ T cells based on higher CD62L, CXCR4 and CCR7 expression. [Cancer Immunol Immunother] Full Article

Peripheral Natural Killer Cells and Myeloid-Derived Suppressor Cells Correlate with Anti-PD-1 Responses in Non-Small Cell Lung Cancer

The authors evaluated the frequencies of T cells, B cells, NK cells, polymorphonuclear myeloid-derived suppressor cells, mononuclear myeloid-derived suppressor cells, and Lox-1⁺ PMN-MDSCs in peripheral blood samples of 62 non-small cell lung cancer patients before and after nivolumab treatment. [Sci Rep] Full Article

Protection and Immune Modulation of Activated Human Vaginal Epithelial Cells by Aurea helianthus Extract

Investigators established three immunological functions of the extract. It mediated tumorigenic suppression in human vaginal epithelial cells (HVECs). Expression of cytokeratin 8, cancer antigen-125, and vimentin was dramatically downregulated in HVECs exposed to the extract under oxidative and fungal stresses. [Sci Rep] Full Article

Isolation and Purification of Immune Cells from the Liver

Scientists compared mechanical dissection and collagenase digestion, and the results were represented by the proportion of lymphocytes, Kupffer cells and neutrophils. The apoptosis rates of liver immune cells resulted by different isolation protocols were compared by Annexin V-staining using flow cytometric analysis. [Int Immunopharmacol] Abstract

Non-Signaling Chimeric Antigen Receptors (NSCARs) Enhance Antigen-Directed Killing by γδ T Cells in Contrast to αβ T Cells

Scientists expressed NSCARs in γδ T cells since donor-derived γδ T cells could be used to prevent product contamination, and NSCARs lacked signaling/activation domains, but retained antigen-specific tumor cell-targeting capability. [Mol Ther Oncolytics] Abstract | Full Article | Graphical Abstract

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The Adenosine Pathway in Immuno-Oncology

With several clinical trials currently evaluating inhibitors of the extracellular adenosine (eADO) pathway in patients with cancer, the authors review the pathophysiological function of eADO with a focus on effects on antitumour immunity. [Nat Rev Clin Oncol] Abstract

Human Monocyte Subset Distinctions and Function: Insights from Gene Expression Analysis

Investigators evaluated the insights into subset functional distinctions that have been garnered from monocyte gene expression analysis and the potential utility of such studies to unravel subset-specific functional changes which arise in disease states. [Front Immunol] Full Article

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UbiVac Announces Clinical Trial Collaboration with Bristol Myers Squibb on Combination Immunotherapy for Advanced Triple Negative Breast Cancer

UbiVac, Inc. announced it has entered into a clinical trial collaboration with Bristol Myers Squibb to evaluate the safety, tolerability, and preliminary efficacy of UbiVac’s investigational product, DPV-001™, a first-in-class cancer vaccine that exploits autophagy, in combination with Bristol Myers Squibb’s anti-OX40 combined with sequenced administration of the programmed death-1 immune checkpoint inhibitor, Opdivo. [UbiVac, Inc.] Press Release

DS Biotech Announces Clinical Trial of Its Lead Immunotherapy Product, PDS0101, in Combination with Chemoradiotherapy in Advanced Cervical Cancer

PDS Biotechnology Corporation announced a Phase II clinical trial to evaluate its lead immunotherapy product, PDS0101, in combination with standard of care chemoradiotherapy for treatment of locally advanced cervical cancer. [PDS Biotechnology Corporation] Press Release

Nobel Laureate Tasuku Honjo to Sue Japanese Drug Firm for 22 billion Yen

In another high-profile case of a Japanese scientist fighting for a share of the profits generated by a key discovery, Nobel laureate Tasuku Honjo announced he plans to sue Osaka, Japan-based Ono Pharmaceutical for 22 billion yen, which he believes he should get for supporting the drug firm in a patent dispute. [ScienceInsider] Editorial

As Pandemic Pounds US Universities, Federal Support Helps Their Labs Stay Afloat

This spring, as the coronavirus pandemic shuttered US higher education, many college presidents began to warn of the dire financial impact of a frozen US economy on their institutions. Their mix of revenue sources largely determined how much they might be hurt. [ScienceInsider] Editorial

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NEW Research Scientist – Tumor Immunology (Northwestern University)

NEW Postdoctoral Fellow – Immune and Stem Cell Engineering (Terasaki Institute for Biomedical Innovation)

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.)

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