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Review
. 2024 Sep;13(17):e70164.
doi: 10.1002/cam4.70164.

Human TCR repertoire in cancer

Lin Chen  1   2 , Yuan Hu  2   3 , Bohao Zheng  2   4   5 , Limei Luo  6 , Zhenzhen Su  6
Affiliations
Review

Human TCR repertoire in cancer

Lin Chen et al. Cancer Med. 2024 Sep.

Abstract

Background: T cells, the "superstar" of the immune system, play a crucial role in antitumor immunity. T-cell receptors (TCR) are crucial molecules that enable T cells to identify antigens and start immunological responses. The body has evolved a unique method for rearrangement, resulting in a vast diversity of TCR repertoires. A healthy TCR repertoire is essential for the particular identification of antigens by T cells.

Methods: In this article, we systematically summarized the TCR creation mechanisms and analysis methodologies, particularly focusing on the application of next-generation sequencing (NGS) technology. We explore the TCR repertoire in health and cancer, and discuss the implications of TCR repertoire analysis in understanding carcinogenesis, cancer progression, and treatment.

Results: The TCR repertoire analysis has enormous potential for monitoring the emergence and progression of malignancies, as well as assessing therapy response and prognosis. The application of NGS has dramatically accelerated our comprehension of TCR diversity and its role in cancer immunity.

Conclusions: To substantiate the significance of TCR repertoires as biomarkers, more thorough and exhaustive research should be conducted. The TCR repertoire analysis, enabled by advanced sequencing technologies, is poised to become a crucial tool in the future of cancer diagnosis, monitoring, and therapy evaluation.

Keywords: T‐cell receptor; cancer; immunotherapy; next‐generation sequencing.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
αβT cell development. Lymphoid precursors derived from bone marrow travel to the thymus. These double‐negative (DN) early T cells express neither CD4 nor CD8 and can be subdivided into four stages of differentiation. During lymphocyte development, specificity and diversity result from the V(D)J recombination of distinct variable (V), diversity (D), and joining (J) gene segments. At the DN3 stage, T cell development begins with the joining of D and J gene segments for the TCRβ chain. The V gene segment is joined at the DN4 stage. Each join in the process is preceded by a random insertion or deletion of nucleotides at the junctions. Cells that express a pre TCR consisting of a functional TCRβ chain and an invariant pre TCRα chain proceed to the subsequent stage of development, whereas cells lacking pre TCR undergo apoptosis. The remaining cells undergo ligand‐independent and ligand‐dependent expansion, and TCRα rearrangement including VJ recombination, resulting in expression of TCRs and double positive of CD4 and CD8 (DP). The cells without TCR expression, with TCR that does not recognize self‐major histocompatibility complex (self‐MHC) molecules and with TCR that has excessive affinity for self‐peptide–MHC complex would die (positive selection and negative selection). The remaining cells with TCRαβ and single positive (SP) become naive αβT cells.
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