γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the ...γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the antitumor immune response.In this study,we characterized the pattern of the human TCRγδcomplementary determinant region 3(CDR3)repertoire in patients with lung carcinoma(LC)via high-throughput sequencing.The results showed that the diversity of CDR3δwas significantly reduced,and that of CDR3γwas unchanged in LC patients compared with healthy individuals;in addition,LC patients shared significantly more CDR3δsequences 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 TCRγδrepertoire features that focus on CDR3δand can be used as a biomarker for LC diagnosis.Our research suggests that the TCRγδCDR3 repertoire changed in LC patients due to the antitumor immune response byγδT cells in vivo,and these changes primarily focus on the amplification of certain tumor-specific CDR3δclones among patients.This study demonstrates the role ofγδT cells from the TCRγδCDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function ofγδT cells in antitumor immunity.展开更多
基金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)+2 种基金the CAMS Initiative for Innovative Medicine(2016-I2M-1-008)the National Key Research and Development Program of China(2016YFA0101001,2016YFC0903900)Peking Union Medical College Foundation(No.3332015111).
文摘γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the antitumor immune response.In this study,we characterized the pattern of the human TCRγδcomplementary determinant region 3(CDR3)repertoire in patients with lung carcinoma(LC)via high-throughput sequencing.The results showed that the diversity of CDR3δwas significantly reduced,and that of CDR3γwas unchanged in LC patients compared with healthy individuals;in addition,LC patients shared significantly more CDR3δsequences 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 TCRγδrepertoire features that focus on CDR3δand can be used as a biomarker for LC diagnosis.Our research suggests that the TCRγδCDR3 repertoire changed in LC patients due to the antitumor immune response byγδT cells in vivo,and these changes primarily focus on the amplification of certain tumor-specific CDR3δclones among patients.This study demonstrates the role ofγδT cells from the TCRγδCDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function ofγδT cells in antitumor immunity.