Tu205 - Using a Consensus Gene Signature to Systematically Annotate Exhausted T-cells

Abstract Text: The exhaustion of T cells is prompted by chronic antigen stimulation and is characterized by terminal loss of effector T-cell capabilities. T-cell exhaustion has been mostly studied in the context of chronic inflammation and cancers, where exhaustion is pathogenic due to defective T cell immunosurveillance function. Recently, studies have highlighted T-cell exhaustion in the context of autoimmune conditions, demonstrating that exhaustion is associated with increased flare-free survival time and slower disease progression.

A challenge in studying the process of T-cell exhaustion is the lack of unified approach of annotating the T-cell exhausted state. We have curated a list of T-cell exhaustion marker genes and used SARGENT, a gene-signature cluster-free based approach, to annotate T-cells in publicly available cancer and immune-diseases datasets. We next used this approach to annotate T-cells that have been exhausted using a re-stimulation by CD3/CD28. In-vitro stimulation of T-cells led to an increase in exhausted T-cells. Moreover, multiple stimulations increased the proportion of exhausted T-cells, suggesting that our annotation strategy accurately highlights exhausted T-cells.

Taken together, our unified annotation approach and an established T-cell exhaustion assay will allow us to investigate the dynamics of T-cell exhaustion and derive conclusions that could be translated to disease datasets.