Luo Wei, He Wen-Ting, Wen Qian, Chen Shu, Wu Jing, Chen Xiang-Ping, Ma Li
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University Guangzhou 510515, China.
Cancer Research Institute, Foshan First People's Hospital Foshan, Guangdong 528000, China.
Am J Cancer Res. 2014 Nov 19;4(6):924-33. eCollection 2014.
We have previous found a positive correlation between post-therapy TCR repertoire normalization and remission of colorectal cancer (CRC) patients following fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or Rh-endostatin therapy. To further define the TCR repertoire diversity changes following treatment in CRC patients, and confirm its potential prognostic value, the present study extended the sample size of follow-up and used an alternative therapy regime to investigate changes of TCR repertoires following Erbitux plus FOLFIRI therapy. Inclusion and exclusion criteria have been established to screen out 26 patients to receive Erbitux plus FOLFIRI therapy. Efficacy and toxicity assessment have been made for them after 3 months' treatment as well as the TCR repertoire diversity has been determined. A CDR3 complex scoring system was used to quantify the diversity of TCR repertoire. The results showing that the diversity of CD4(+) T cells in PR group was significantly higher than that of SD and PD groups, and the difference was enlargement after treatment. The diversity of CD8(+) T cells in PR group has no difference before and after treatment, but significant decrease in SD and PD group after treatment. In conclusion, analysis the diversity of T cell repertoire has an important prognosis value for CRC patients.
我们之前发现，在接受氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合贝伐单抗或重组人血管内皮抑制素治疗的结直肠癌（CRC）患者中，治疗后TCR库正常化与缓解之间存在正相关。为了进一步明确CRC患者治疗后TCR库多样性的变化，并确认其潜在的预后价值，本研究扩大了随访样本量，并采用另一种治疗方案来研究西妥昔单抗联合FOLFIRI治疗后TCR库的变化。已制定纳入和排除标准，筛选出26例患者接受西妥昔单抗联合FOLFIRI治疗。在治疗3个月后对他们进行了疗效和毒性评估，并确定了TCR库多样性。使用CDR3复合体评分系统对TCR库的多样性进行量化。结果显示，PR组中CD4(+) T细胞的多样性显著高于SD组和PD组，且治疗后差异增大。PR组中CD8(+) T细胞的多样性在治疗前后无差异，但SD组和PD组在治疗后显著降低。总之，分析T细胞库的多样性对CRC患者具有重要的预后价值。
