Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy

The T-cell receptor (TCR) repertoire, representing the vast diversity of T cells, is a cornerstone of adaptive immunity and a powerful tool in oncology. Advances in high-throughput sequencing have enabled deep profiling of TCR diversity and clonality, highlighting the repertoire as a promising biomarker for cancer diagnosis, prognosis and therapeutic monitoring. This review synthesizes the current understanding of TCR repertoire analysis in cancer care. Distinct TCR features in tumors and peripheral blood can differentiate cancer patients from healthy individuals and help stage disease. Prognostically, a focused, clonal intratumoral repertoire is often associated with improved survival, whereas high diversity in peripheral blood typically reflects robust immune competence and better outcomes. In cancer immunotherapy, TCR profiling offers predictive insights; high baseline tumor clonality frequently correlates with response to anti-programmed cell death protein 1/programmed death-ligand 1 inhibitors, while greater peripheral diversity may predict benefit from anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) therapy. Dynamic monitoring often shows an increase in clonality in patients responding to treatment. Furthermore, TCR analysis is integral to optimizing and tracking adoptive cell therapies and cancer vaccines. Despite this potential, significant challenges, including a lack of methodological standardization, currently limit widespread clinical application. Integrating TCR analysis with multi-omic and single-cell technologies is essential to overcoming these hurdles and advancing personalized immunotherapy.