肝癌肝移植术后西罗莫司转换治疗的免疫学效应分析

Immunological Effect of Sirolimus Conversion Therapy on Hepatic Carcinoma after Liver Transplantation

目的探讨以西罗莫司为主的联合免疫治疗方案(SCTR)对肝癌肝移植受者体内调节性T细胞(Treg)和效应性T细胞表达的影响。方法对2010年1月—2015年6月收治的应用SCTR干预的肝癌肝移植28例的临床资料进行回顾性分析,观察术后不同时间点CD3、CD8+的表达,并对其与Treg的表达进行相关性分析。结果 SCTR干预下,肝癌肝移植受者术后12个月内,Fox P3+Treg的比例从术前峰值降低到术后1个月谷值,随后逐渐升高,3个月时在正常值水平(P>0.05),术后12~18个月水平逐步维持在较低水平,与正常水平比较差异有统计学意义(P<0.05)。术前、术后12和18个月Fox P3+Treg和CD3、CD8+T淋巴细胞的变化呈反向趋势。Fox P3+Treg与CD3和CD8的表达水平呈负相关(r=-6.37、-7.12,P<0.001)。肝癌肝移植术后白介素-10、β型转化生长因子和甲胎蛋白水平均较术前显著降低(P<0.05),且其变化与Treg呈正相关。结论 SCTR可降低肝癌肝移植术后Fox P3+Treg、IL-10、TGF-β的表达,并不增加排斥反应,临床应用安全、有效。

Objective To investigate effects of Sirolimus combined immune therapy （SCTR） on regulation T cells （Treg） and effector T cells （Teff） expressions in liver transplantation recipients with hepatic carcinoma. Methods Clinical data of 28 hepatic carcinoma patients with liver transplantation treated by SCTR during January 2010 and June 2015 was retrospectively analyzed, and CD3 and CD8 ＋ expressions at postoperatively different time points were observed, and correlation with Treg expression was analyzed. Results By SCTR intervention, the FoxP3＋ Treg ratio was reduced from the peak before surgery to the valley vale 1 month after surgery within 12 months in liver transplantation recipients with hepatic carcinoma, and the ratio increased gradually after that, and then the normal level reached in 3rd month （P 〉 0. 05 ） , and then the ratio maintained at a low level during 12^th-18^th months after surgery, and the difference was statistically significant compared with the normal level （P 〈 0. 05 ）. Changes of CD3 ＋ and CD8 ＋ T-lymphoeytes showed a reverse trend with FoxP3 ＋ Treg before and in 12^th-18^th months after surgery. FoxP3 ＋ Treg expression showed negative correlation with CD3 and CD8 expressions （ r =-6.37,-7. 12, P 〈 0. 001 ）. Levels of interleukin-10 （ IL-10） , transforming growth factor-β （TGF-[3） and alpha-fetoprotein were significantly decreased after liver transplantation compared with those before transplantation （P 〈 0.05） , and the changes were positively correlated with Treg. Conclusion SCTR can decrease FoxP3 ＋ Treg, IL-10 and TGF-β expressions without increasing rejection reaction in liver trans- plantation patients with hepatic carcinoma, and therefore it is safe and effective in clinic.