TCR-sequencing in cancer and autoimmunity: barcodes and beyond.

The T cell receptor (TCR) endows T cells with antigen specificity and is central to nearly all aspects of T cell function. Each naïve T cell has a unique TCR sequence that is stably maintained during cell division. In this way, the TCR serves as a molecular barcode that tracks processes such as migration, differentiation, and proliferation of T cells. Recent technological advances have enabled sequencing of the TCR from single cells alongside deep molecular phenotypes on an unprecedented scale. In this review, we discuss strengths and limitations of TCR sequences as molecular barcodes and their application to study immune responses following Programmed Death-1 (PD-1) blockade in cancer. Additionally, we consider applications of TCR data beyond use as a barcode. The T cell receptor (TCR) can act as a molecular barcode in mice and humans to track T cells with clonal-relatedness through processes such as migration, differentiation, and proliferation. The TCR sequence provides a means to enrich T cells of interest in diverse types of cancer and some types of autoimmunity. Using the TCR as a barcode in cancer has been useful for identifying mechanisms of Programmed Death-1 (PD-1) blockade-based immunotherapy and features associated with clinical responses in diverse cancer types. Using the TCR sequence to identify T cell populations of interest is currently limited by our inability to confidently infer antigen-specificity from the TCR sequence. Beyond acting as a molecular-identity barcode, the TCR sequence consists of a set of features that can inform T cell fate and function. [ABSTRACT FROM AUTHOR]