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T cell receptor β‐chain repertoire analysis reveals the association between neoantigens and tumour‐infiltrating lymphocytes in multifocal papillary thyroid carcinoma
Authors:Zheming Lu  Jindong Sheng  Jing Shen  Baoguo Liu
Affiliation:1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, ChinaZ.L. and C.Z. contributed equally to this work;2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Head & Neck Surgery, Peking University Cancer Hospital & Institute, Beijing, China;3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Core laboratory, Peking University Cancer Hospital & Institute, Beijing, China
Abstract: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.
Keywords:high‐throughput sequencing  T cell receptors  neoantigens  tumour‐infiltrating lymphocytes  multifocal papillary thyroid carcinoma
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