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

• Published in: International journal of cancer 2017-07, Vol.141 (2), p.377-382
• Main Authors: Lu, Zheming, Zhang, Chaoting, Sheng, Jindong, Shen, Jing, Liu, Baoguo
• Format: Article
• Language: English
• Subjects: Carcinoma - genetics; Carcinoma - immunology; Carcinoma, Papillary; High-Throughput Nucleotide Sequencing; high‐throughput sequencing; Humans; Lymphocytes, Tumor-Infiltrating - immunology; multifocal papillary thyroid carcinoma; Mutation; neoantigens; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Sequence Analysis, DNA; T cell receptors; Thyroid Cancer, Papillary; Thyroid Neoplasms - genetics; Thyroid Neoplasms - immunology; tumour‐infiltrating lymphocytes
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30743

To explore whether a few nonsynonymous 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 noncontiguous cancer foci) to investigate the relationship between neoantigens and TILs. These seven foci had a few or no nonsynonymous 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 nonsynonymous 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 nonsynonymous somatic mutations is small in tumours with low mutation rates but these mutations still play an important role in activating neoantigen‐specific TILs. What's new? Cancer neoantigens, which arise via non‐synonymous somatic mutations, represent attractive targets for immunotherapy. Here, the authors explored 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. They found in multifocal papillary thyroid carcinoma that 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. While the number of non‐synonymous somatic mutations is small in tumours with low mutation rates, these can still play an important role in activating neoantigen‐specific TILs.