4.6 Review

TCR-sequencing in cancer and autoimmunity: barcodes and beyond

Journal

TRENDS IN IMMUNOLOGY
Volume 43, Issue 3, Pages 180-194

Publisher

CELL PRESS
DOI: 10.1016/j.it.2022.01.002

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Categories

Funding

  1. National Institute of General Medical Sciences [T32GM007753]
  2. National Cancer Institute [T32 CA233414]
  3. Yale SPORE in Skin Cancer [P50 CA121974]
  4. National Institutes of Health [P50 CA121974, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, R01 CA227473, P01 AI039671, P01 AI056299, P01 CA236749, P01 AI108545, 1P01AI148102-01A1, 1U01HG012009-01, 2R01AR063759-06A1]
  5. Merck
  6. Novartis
  7. Genentech/Roche
  8. Seagen
  9. Incyte
  10. BMS
  11. Parker Institute for Cancer Immunotherapy
  12. Amoroso Fund
  13. Cook Fund
  14. McGlynn Fund

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The T cell receptor serves as a molecular barcode tracking T cell functions and immune responses. Recent technological advances allow for single-cell TCR sequencing on an unprecedented scale.
The T cell receptor (TCR) endows T cells with antigen specificity and is central to nearly all aspects of T cell function. Each naive 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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