Revealing Clonal Responses of Tumor-Reactive T-Cells Through T Cell Receptor Repertoire Analysis

Abstract

CD8⁺ T cells are the key effector cells that contribute to the antitumor immune response. They comprise various T-cell clones with diverse antigen-specific T-cell receptors (TCRs). Thus, elucidating the overall antitumor responses of diverse T-cell clones is an emerging challenge in tumor immunology. With the recent advancement in next-generation DNA sequencers, comprehensive analysis of the collection of TCR genes (TCR repertoire analysis) is feasible and has been used to investigate the clonal responses of antitumor T cells. However, the immunopathological significance of TCR repertoire indices is still undefined. In this review, we introduce two approaches that facilitate an immunological interpretation of the TCR repertoire data: inter-organ clone tracking analysis and single-cell TCR sequencing. These approaches for TCR repertoire analysis will provide a more accurate understanding of the response of tumor-specific T cells in the tumor microenvironment.

Keywords: CD8+ T cell; T-cell receptor repertoire; cancer-immunity cycle; immune check inhibitors; inter-organ clone tracking; single-cell TCR-seq.