T cell receptor β-chain repertoire analysis reveals the association between neoantigens and tumour-infiltrating lymphocytes in multifocal papillary thyroid carcinoma

Abstract

To explore whether a few non-synonymous somatic mutations could induce activation and proliferation of neoantigen-specific tumour-infiltrating lymphocytes (TILs) in tumours with low mutation rates, we analysed a patient with multifocal papillary thyroid carcinoma (seven non-contiguous cancer foci) to investigate the relationship between neoantigens and TILs. These seven foci had a few or no non-synonymous somatic mutations; moreover, multiple loci had similar or different spectra of mutations. We used high-throughput sequencing of the rearranged genes in T cell receptor β-chain (TCRβ) to reveal the basic characteristics of T cells in seven tumour foci and matched adjacent normal tissue. We found that in multifocal papillary thyroid carcinoma the number of non-synonymous somatic mutations was positively associated with oligoclonal TCRβ repertoire, and tumour foci with similar spectra of mutations had higher overlap of TCRβ repertoire. In conclusion, the number of non-synonymous somatic mutations is small in tumours with low mutation rates but these mutations still play an important role in activating neoantigen-specific TILs. This article is protected by copyright. All rights reserved.

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