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The Dynamic Characteristics of TCR β CDR3 Repertoire of Peripheral Blood T Cells Before and After Chemotherapy in the Early Stage of Breast Cancer Patients
Yang Liwen1#, Sun Suhong2#, Zhang Tian1#, Duan Fangfang1, He Xiaoyan1, Ma Rui1, Ma Long1, Shi Bin3, Yao Xinsheng1*
1Department of Immunology, Research Center for Medicine & Biology, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi 563003, China; 2Department of Breast Surgery, the First Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China; 3Department of Laboratory Medicine, Zunyi Medical University, Zunyi 563003, China
Abstract: Using high-throughput sequencing (HTS) technology， analysis of the dynamic change characteristics and composition of T cell of T-cell receptor beta chain complementarity determining region 3 (TCR β CDR3) repertoire in peripheral blood before and after chemotherapy with breast cancer patients in the early period， preliminary discussion on the possible effect of chemotherapy on T cells and T cell response function status before and after chemotherapy patients. The pathological biopsy diagnosed patients with T1N0M0 breast cancer as the research object， a six periods TAC (T: docetaxel; A: pirarubicin; C: cyclophosphamide) chemotherapy in three volunteers patients (P1， P2， P3)， before chemotherapy， after the third periods of chemotherapy and the sixth periods of chemotherapy， then collected the peripheral blood and separated the PBMC， respectively， and extracted genomic DNA. Using the multiple PCR to construct human TCR β CDR3 repertoire and HTS， then using Immuno SEQ and IMGT-High-V-QUEST analysis the composition and characteristics of TCR β CDR3 sequences. The results suggest that after the third period of treatment， CDR3 repertoire diversity (the inverse Simpson index) was higher than before chemotherapy in P1， P2， P3. After the six period of treatment， compared with the third period of treatment， CDR3 repertoire diversity decreased in P1 and P3， but increased in P2. After the third period of treatment， in P1 and P3 patients， CDR3 repertoire highfrequency clones (greater than 1%) lower than the chemotherapy before. And after the sixth period of treatment， CDR3 repertoire high-frequency clones increased significantly compared with the third treatment. In P2 patient， there was no changes in the high-frequency clones in CDR3 repertoire after the third period of treatment compared with before chemotherapy， but after the sixth period of treatment， it was significantly reduced. The partial TRBV gene usage was lost and reused before and after chemotherapy in P1 and P2， and the TRBV gene usage of P3 did not change significantly; the partial TRBV and TRBJ advantage pairing were disappeared after chemotherapy in P2 and P3. In conclusion， the early breast cancer patients before， during and after TAC chemotherapy which the peripheral blood T cells TCR β CDR3 repertoire had a variety of individualized and characteristic changes， it may be associated with TAC suppression or killing of individual T cells， the composition and dynamic changes of CDR3 repertoire can be used to provide a basis for the effects of chemotherapy on T cells and the “individualized” T cell immune status assessment before and after chemotherapy.
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