Longitudinal High-Throughput Sequencing of the T-Cell Receptor Repertoire Reveals Dynamic Change and Prognostic Significance of Peripheral Blood TCR Diversity in Metastatic Colorectal Cancer During Chemotherapy

Frontiers in Immunology

Immunology

Yun-Shien Lee¹  Hung-Chih Hsu²  Chia-Yin Chin³  Hsuan Liu⁴  Ian Yi-Feng Chang⁵  Chia-Yu Yang⁶  Yi-Tung Chen⁷  Bertrand Chin-Ming Tan⁸ 

[1] Department of Biotechnology, Ming Chuan University, Taoyuan, Taiwan;Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan;College of Medicine, Chang Gung University, Tao-Yuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan;Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan;Department of Neurosurgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan;Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan;Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Neurosurgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan;

关键词: T cell repertoire;    metastatic colorectal cancer;    prognosis;    peripheral blood;    chemotherapy;   

DOI  :  10.3389/fimmu.2021.743448

 received in 2021-07-18, accepted in 2021-12-20,  发布年份 2022

来源: Frontiers

【 摘 要 】

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment.

【 授权许可】

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Copyright © 2022 Chen, Hsu, Lee, Liu, Tan, Chin, Chang and Yang