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 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.

Characteristics and prognostic significance of profiling the peripheral blood T‐cell receptor repertoire in patients with advanced lung cancer

“…Our knowledge of the TCR patterns in lung cancer is very limited. The TCR repertoire is heterogeneous, differing between regions within the same tumor in lung cancer and many other malignancies . Furthermore, tumor tissue is difficult to obtain and dynamically monitor, especially in patients with advanced disease.…”

“…7,[16][17][18][19][20][21][22] Moreover, the existence of differences in TCR patterns between cancers and tissue or blood samples highlight the necessity of additional detailed studies for specific malignancies, at both the baseline and treatmentresponse levels. [13][14][15]20,[22][23][24][25][26][27] Our knowledge of the TCR patterns in lung cancer is very limited. The TCR repertoire is heterogeneous, differing between regions within the same tumor in lung cancer and many other malignancies.…”

“…The TCR repertoire is heterogeneous, differing between regions within the same tumor in lung cancer and many other malignancies. 13,15,[24][25][26][27][28] Furthermore, tumor tissue is difficult to obtain and dynamically monitor, especially in patients with advanced disease. The use of blood samples is an attractive alternative to overcome these problems.…”

TCR repertoire intratumor heterogeneity of CD4+ and CD8+ T cells in centers and margins of localized lung adenocarcinomas

“…Details of TCRβ sequencing were delineated in our previous studies . In Brief, the CDR3 region of TCRβ chain was amplified using Multiplex PCR and ultradeep sequenced using the Illumina Hiseq2500 platform (MyGenostics, Beijing, China) from approximately 1 μg of genomic DNA for each sample.…”

“…To quantify the diversity of TCR repertoire, we adopted clonality index which provides a diversity measurement as a function of distribution of TCR frequencies and is independent of sampling depth. The clonality is defined as 1—normalized Shannon's entropy with values ranging from 0 (most diverse) to 1 (least diverse) …”