Profiling the pattern of the human T-cell receptor γδ complementary determinant region 3 repertoire in patients with lung carcinoma via high-throughput sequencing analysis

gamma delta T cells function as sentinels in early host responses to infections and malignancies. Specifically, gamma delta T cells recognize tumor-associated stress antigens via T-cell receptor (TCR) gamma delta and play important roles in the antitumor immune response. In this study, we characterized the pattern of the human TCR gamma delta complementary determinant region 3 (CDR3) repertoire in patients with lung carcinoma (LC) via high-throughput sequencing. The results showed that the diversity of CDR3 delta was significantly reduced, and that of CDR3 gamma was unchanged in LC patients compared with healthy individuals; in addition, LC patients shared significantly more CDR3 delta sequences with each other than healthy individuals. The CDR3 length distribution and N-addition length distribution did not significantly differ between LC patients and healthy individuals. In addition, the CDR3 repertoire tended to use more V delta 2 and fewer V delta 1 germline gene fragments among LC patients. Moreover, we found a combination of four TCR gamma delta repertoire features that focus on CDR3 delta and can be used as a biomarker for LC diagnosis. Our research suggests that the TCR gamma delta CDR3 repertoire changed in LC patients due to the antitumor immune response by gamma delta T cells in vivo, and these changes primarily focus on the amplification of certain tumor-specific CDR3 delta clones among patients. This study demonstrates the role of gamma delta T cells from the TCR gamma delta CDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function of gamma delta T cells in antitumor immunity.