TCR-sequencing in cancer and autoimmunity: barcodes and beyond

Kristen E Pauken; Kaitlyn A Lagattuta; Benjamin Y Lu; Liliana E Lucca; Adil I Daud; David A Hafler; Harriet M Kluger; Soumya Raychaudhuri; Arlene H Sharpe

doi:10.1016/j.it.2022.01.002

TCR-sequencing in cancer and autoimmunity: barcodes and beyond

Trends Immunol. 2022 Mar;43(3):180-194. doi: 10.1016/j.it.2022.01.002. Epub 2022 Jan 25.

Authors

Kristen E Pauken¹, Kaitlyn A Lagattuta², Benjamin Y Lu³, Liliana E Lucca⁴, Adil I Daud⁵, David A Hafler⁶, Harriet M Kluger⁷, Soumya Raychaudhuri⁸, Arlene H Sharpe⁹

Affiliations

¹ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Electronic address: kristen_pauken@hms.harvard.edu.
² Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
³ Department of Neurology and Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
⁴ Department of Neurology and Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
⁵ Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁶ Department of Neurology and Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁷ Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
⁸ Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Centre for Genetics and Genomics Versus Arthritis, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PL, UK.
⁹ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: arlene_sharpe@hms.harvard.edu.

Abstract

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.

Keywords: PD-1 immunotherapy; T cell; TCR sequencing; cancer; molecular barcode; single cell sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Autoimmunity* / genetics
Humans
Neoplasms* / genetics
Receptors, Antigen, T-Cell / genetics
T-Lymphocytes

Substances

Receptors, Antigen, T-Cell

Abstract

Publication types

MeSH terms

Substances

Grants and funding