γδ T cells function as sentinels in early host responses to infections and malignancies. Specifically, γδ T cells recognize tumor-associated stress antigens via T-cell receptor (TCR) γδ and play important roles in the antitumor immune response. In this study, we characterized the pattern of the human TCR γδ complementary determinant region 3 (CDR3) repertoire in patients with lung carcinoma (LC) via high-throughput sequencing. The results showed that the diversity of CDR3δ was significantly reduced, and that of CDR3γ was unchanged in LC patients compared with healthy individuals; in addition, LC patients shared significantly more CDR3δ 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 Vδ2 and fewer Vδ1 germline gene fragments among LC patients. Moreover, we found a combination of four TCR γδ repertoire features that focus on CDR3δ and can be used as a biomarker for LC diagnosis. Our research suggests that the TCR γδ CDR3 repertoire changed in LC patients due to the antitumor immune response by γδ T cells in vivo, and these changes primarily focus on the amplification of certain tumor-specific CDR3δ clones among patients. This study demonstrates the role of γδ T cells from the TCR γδ CDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function of γδT cells in antitumor immunity.
This work was supported by the National Natural Science Foundation of China (31500725, 81673010, 91542117, 81471574, 31471016), CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses (2016ZX310180-5 and 2017PT31004), the CAMS Initiative for Innovative Medicine (2016-I2M-1-008), the National Key Research and Development Program of China (2016YFA0101001, 2016YFC0903900) and Peking Union Medical College Foundation (No. 3332015111). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Dr Austin Cape at ASJ Editors for the editing and comments.