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.

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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