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Trends in Immunology
Volume 43 (3), 2022, Pages 180-194

TCR-sequencing in cancer and autoimmunity: barcodes and beyond

Kristen E. Pauken1,2, Kaitlyn A. Lagattuta3.4,5,14

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.


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.

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