Table_5_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.xlsx

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.

结直肠癌（Colorectal cancer, CRC）是癌症相关死亡与发病的主要诱因之一。尽管化疗与靶向治疗取得了进展，但由于肿瘤复发与治疗耐药，临床获益难以持续。癌症患者的免疫状态可能影响疾病治疗的效果。T细胞受体（T-cell receptor, TCR）库的动态变化或可作为监测治疗响应的临床参数。
本研究旨在探讨不可切除转移性结直肠癌（metastatic colorectal cancer, mCRC）患者的TCR库特征及其临床意义。本研究共纳入20名健康对照者与16名CRC患者的103份外周血样本，随访时长为98至452天，通过高通量测序技术对TCRα与TCRβ库的高变重排进行全面分析。
研究发现，与健康对照相比，mCRC患者的TCRα库、TCRβ库以及CDR3克隆型均发生改变。多数mCRC患者在接受治疗后，TCR库与CDR3克隆型的多样性有所下降。进一步分析显示，与基线TCR多样性相比，治疗期间TCR多样性显著下降的患者展现出更优的治疗响应，包括更低的癌胚抗原（CEA）与糖链抗原19-9（CA19-9）水平以及更小的肿瘤体积。基线TCR多样性同样与部分缓解（partial response, PR）状态显著相关（优势比：5.29，p=0.04）。
综上，本研究证实了化疗期间TCR多样性的动态变化与临床结局之间存在关联，并揭示了TCR库在预测癌症治疗预后方面的潜在应用价值。