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Updated: Mar 9, 2026

T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
T cell receptor repertoire usage in cancer as a surrogate marker for immune responses
David Schrama1, Cathrin Ritter2,3,4, Jürgen C Becker5,6,7
1Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
Abstract:
Characterizing the interaction of cancer cells with the host adaptive immune system is critical for understanding tumor immunology and the modus operandi of immunotherapeutic interventions to treat cancer. As the key cellular effectors of adaptive immunity, T cells are endowed with specialized receptors (the T cell receptor; TCR), to recognize and to eliminate cancer cells. The diversity of the TCR repertoire results from specialized genetic diversification mechanisms that generate an incredible variability allowing recognizing extensive collections of antigens. Based on the attainment and function of the TCR, the TCR repertoire is a mirror of the human immune response, and the dynamic changes of its usage can be assumed as a promising biomarker to monitor immunomodulatory therapies. Recent advances in multiplexed PCR amplification and massive parallel sequencing technologies have facilitated the characterization of TCR repertoires at high resolution even when only biomaterial of limited quantity and quality, such as formalin-fixed paraffin-embedded (FFPE) archived tissues, is available. Here, we review the concept framework and current experimental approaches to characterize the TCR repertoire usage in cancer including inherent technical and biological challenges.
Insights
Understanding T cell receptor (TCR) repertoire dynamics in cancer is key for immunotherapy. High-resolution sequencing of TCRs, even from FFPE tissues, offers insights into immune responses and biomarkers for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The interaction between cancer cells and the host adaptive immune system is crucial for tumor immunology and cancer immunotherapy.
- T cells, via their T cell receptors (TCRs), recognize and eliminate cancer cells, with TCR repertoire diversity enabling broad antigen recognition.
- TCR repertoire dynamics serve as a potential biomarker for monitoring immunomodulatory therapies.
Purpose of the Study:
- To review the conceptual framework and current experimental approaches for characterizing T cell receptor (TCR) repertoire usage in cancer.
- To highlight the significance of TCR repertoire analysis in understanding tumor immunology and guiding cancer immunotherapy.
- To discuss the challenges associated with TCR repertoire characterization in the context of cancer research.
Main Methods:
- Utilizing multiplexed PCR amplification and massive parallel sequencing technologies for high-resolution TCR repertoire characterization.
- Analyzing TCR repertoires from limited and low-quality biomaterials, including formalin-fixed paraffin-embedded (FFPE) archived tissues.
- Reviewing existing experimental methodologies for assessing TCR repertoire diversity and usage in cancer patients.
Main Results:
- Recent technological advancements enable high-resolution TCR repertoire profiling even from challenging FFPE samples.
- TCR repertoire analysis provides a dynamic view of the immune response against cancer.
- The findings underscore the potential of TCR repertoire as a biomarker in cancer immunotherapy.
Conclusions:
- Characterizing the TCR repertoire is essential for advancing tumor immunology and cancer immunotherapy.
- High-throughput sequencing technologies have overcome previous limitations in analyzing TCR repertoires from archival tissues.
- Further research into TCR repertoire usage can lead to improved biomarkers and therapeutic strategies for cancer treatment.
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