Walter and Eliza Hall Institute of Medical Research

About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.

Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis

Abstract: The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival, particularly in triple-negative and HER2-overexpressing BC subtypes1. Although T cells are the predominant TIL population2, the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311 T cells isolated from human BCs and show that significant heterogeneity exists in the infiltrating T cell population. We demonstrate that BCs with a high number of TILs contained CD8+ T cells with features of tissue-resident memory T (TRM) cell differentiation and that these CD8+ TRM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8+ TRM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple-negative breast cancer (TNBC) and provided better prognostication than CD8 expression alone. Our data suggest that CD8+ TRM cells contribute to BC immunosurveillance and are the key targets of modulation by immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of TRM cells will be crucial for successful immunotherapeutic development in BC.

From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline

Abstract: In recent years, RNA sequencing (RNA-seq) has become a very widely used technology for profiling gene expression. One of the most common aims of RNA-seq profiling is to identify genes or molecular pathways that are differentially expressed (DE) between two or more biological conditions. This article demonstrates a computational workflow for the detection of DE genes and pathways from RNA-seq data by providing a complete analysis of an RNA-seq experiment profiling epithelial cell subsets in the mouse mammary gland. The workflow uses R software packages from the open-source Bioconductor project and covers all steps of the analysis pipeline, including alignment of read sequences, data exploration, differential expression analysis, visualization and pathway analysis. Read alignment and count quantification is conducted using the Rsubread package and the statistical analyses are performed using the edgeR package. The differential expression analysis uses the quasi-likelihood functionality of edgeR.

Inducible expression of H-2 and Ia antigens on brain cells.

Abstract: Cells in the brain express unusually low levels of antigens encoded by the major histocompatibility complex (MHC)1,2. This is somewhat surprising as class I (H−2) and class II (Ia) MHC antigens have critical roles in immune responses3. The activation of T lymphocytes is associated with the enhanced expression of these antigens and this effect is mediated by a specific T-cell lymphokine, γ-interferon (IFN-γ)4–17. Here we show that IFN-γ induces a dramatic increase in the expression of H–2 antigens on the cells of the brain. After exposure to IFN-γ in vitro, all surviving cells, including most astrocytes, oligodendrocytes, microglia and at least some neurones, express H–2 antigens. Direct injection of IFN-γ into the brains of mice indicated that H–2 antigens were also induced in vivo. Furthermore, IFN-γ induced Ia antigens on a subpopulation of astrocytes. The induction of H–2 antigens by IFN-γ may render brain cells competent to initiate and participate in immune reactions and may therefore contribute to both immunoprotective and immunopathological responses in the brain.

Cutting Edge: Intravenous Soluble Antigen Is Presented to CD4 T Cells by CD8− Dendritic Cells, but Cross-Presented to CD8 T Cells by CD8+ Dendritic Cells

Abstract: Mouse spleen contains three distinct mature dendritic cell (DC) populations (CD4(+)8(-), CD4(-)8(-), and CD4(-)8(+)) which retain a capacity to take up particulate and soluble AGS: Although the three splenic DC subtypes showed similar uptake of injected soluble OVA, they differed markedly in their capacity to present this Ag and activate proliferation in OVA-specific CD4 or CD8 T cells. For class II MHC-restricted presentation to CD4 T cells, the CD8(-) DC subtypes were more efficient, but for class I MHC-restricted presentation to CD8 T cells, the CD8(+) DC subtype was far more effective. This differential persisted when the DC were activated with LPS. The CD8(+) DC are therefore specialized for in vivo cross-presentation of exogenous soluble Ags into the class I MHC presentation pathway.