Characterization of the T-cell receptor repertoire by deep T cell receptor sequencing in tissues from patients with prostate cancer

摘要

Prostate cancer (PC) is the most prevalent urological cancer in men. T cells serve a central role in the cancer's immunological microenvironment. In the present study, we applied multiplex PCR and Illumina next-generation sequencing to study the clonal diversity of the T-cell receptor (TCR) repertoire in cancer tissues and paracancer tissues from patients with PC. It was found that the TCR repertoire in the PC samples had a notably more skewed clonotype composition, with a greater number of highly expanded clones (HECs) compared with the prostate paracancer samples. The amino acid sequences ATSRVAGETQY (1.008 vs. 0.002%), ATSRTGRWETQY (3.985 vs. 0.007%), ATSDSSDYEQY (12.464 vs. 0.027%), ATSDFRGQPQETQY (2.205 vs. 0.06%), ASSQQDEAF (1.109 vs. 0.002%) and ARPTRTEETQY (1.263 vs. 0.002%) were found to vary markedly between cancer and paracancer tissues, respectively. In conclusion, the present study identified PC-specific HECs, which are critical to improving understanding of the TCR repertoire in PC. This may accelerate the screening process for potential new autoantigens and provide information for generating more effective T cell-targeted diagnostic and therapeutic strategies.