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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
Next-generation TCR sequencing - a tool to understand T-cell infiltration in human cancers
Isabel Poschke1, Michael Flossdorf2, Rienk Offringa1,3
1Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center, Heidelberg, Germany.
Abstract:
Tumour-infiltrating lymphocytes (TILs) are known to mediate potent anti-tumour activity. As T-cell-based therapies start to reach clinical practice, it becomes increasingly important to understand what characterizes a successful anti-tumour T-cell response and to exploit this knowledge for patient stratification. Next-generation sequencing of T-cell receptors (TCRs) promises to provide insights into the complexity of the tumour T-cell infiltrate that go beyond the phenotypic level. A recent study by Chen et al made use of this novel technology to demonstrate that the TIL repertoire of oesophageal squamous cell carcinoma patients is distinct from that of non-tumour sites and is characterized by significant intratumoural heterogeneity. This study illustrates the great potential of the method and addresses several technical and biological hurdles that need to be considered. Careful sampling, normalization, and error correction will be required to optimally use TCR sequencing to answer biological questions and define predictive biomarkers, e.g. for cancer immunotherapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Insights
Next-generation sequencing of T-cell receptors (TCRs) reveals distinct tumour-infiltrating lymphocyte (TIL) repertoires in oesophageal cancer. This approach highlights intratumoural heterogeneity and aids in defining biomarkers for cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Tumour-infiltrating lymphocytes (TILs) are crucial for anti-tumour immunity.
- T-cell-based therapies are advancing, necessitating understanding of effective anti-tumour responses.
- Characterizing the T-cell receptor (TCR) repertoire is key for patient stratification in cancer immunotherapy.
Purpose of the Study:
- To investigate the T-cell receptor repertoire within tumour-infiltrating lymphocytes (TILs) in oesophageal squamous cell carcinoma.
- To assess the potential of next-generation sequencing (NGS) for analyzing TCR diversity and intratumoural heterogeneity.
- To identify challenges and requirements for utilizing TCR sequencing in cancer research and biomarker discovery.
Main Methods:
- Employed next-generation sequencing (NGS) to analyze T-cell receptor (TCR) sequences.
- Compared TCR repertoires between tumour tissues and non-tumour sites.
- Analyzed intratumoural heterogeneity of the TIL repertoire.
Main Results:
- The TIL repertoire in oesophageal squamous cell carcinoma patients is distinct from non-tumour sites.
- Significant intratumoural heterogeneity was observed in the TIL repertoire.
- The study identified technical and biological considerations for TCR sequencing.
Conclusions:
- TCR sequencing offers deep insights into the complexity of tumour-infiltrating lymphocytes beyond phenotypic analysis.
- Careful methodology (sampling, normalization, error correction) is essential for robust TCR sequencing data.
- TCR sequencing holds potential for defining predictive biomarkers for cancer immunotherapy efficacy.
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