胸腺法新为基础的药物治疗对肝移植术后肿瘤复发及相关细胞因子的影响

Influence of thymosin α-1 based anti-tumor therapy on tumor recurrence and cytokine expression in patients after liver transplantation

目的:探讨以胸腺肽联合槐耳颗粒对肝移植术后肿瘤复发及Foxp3+调节性T细胞(Treg细胞)、白介素(interleukin,IL)-10、转化生长因子β(transforming growth factor-β,TGF-β)的表达.方法:从2011-01/2015-01在解放军第309医院接受肝移植的患者中搜集病例数共计42例患者的临床资料(均符合杭州标准),包括肝细胞癌(肝癌)患者42例.根据患者术后用药情况分为联合用药组19例,槐耳颗粒组16例,胸腺法新组7例.术后各组根据个体差异调整免疫抑制剂的种类和剂量[他克莫司(F K506)+吗替麦考酚酯(M M F)+西罗莫司].1 mo后联合用药组采用以胸腺法新联合槐耳颗粒抗肿瘤药物治疗,其他2组分别单用槐耳颗粒及胸腺法新.观察肝癌患者肿瘤的复发时间及各组外周血中调节性T细胞(Treg细胞)、IL-10、TGF-β的表达情况.每例患者的观察时间均为12 mo.结果:联合药物组的无瘤生存时间明显高于槐耳颗粒组及胸腺法新组(P<0.05);术后第6个月联合用药组中Treg细胞和IL-10的表达明显高于胸腺法新组(P<0.05),而联合药物组与胸腺法新组差异无统计学差异(P>0.05).术后第12个月,联合药物组Treg、TGF-β、IL-10的表达明显高于胸腺法新组及槐耳颗粒组(P<0.05).结论:胸腺法新联合槐耳颗粒抗肿瘤疗法可明显延长肝癌肝移植术后肿瘤的复发时间,较单用胸腺法新或者槐耳颗粒有良好的临床效果,术后定期监测Treg细胞、IL-10、TGF-β表达,可作为肝癌肝移植术后肿瘤复发的辅助指标.

AIM： To explore the influence of thymosin α-1 combined with Huaier granule on tumor recurrence and expression of Foxp3~＋ regulatory T（Treg） cells, interleukin-10（IL-10）, and transforming growth factor-β（TGF-β） in patients after liver transplantation.METHODS： Clinical data for 42 patients with terminal primary liver cancer who underwent liver transplantation at the 309 th Hosptial of Chinese People’s Liberation Army from January 2011 to January 2015（all meeting the Hangzhou standard） were retrospectively analyzed. According to postoperative medication, the patients were divided into a combination group（19 cases）, a Huaier granule group（16 cases） and a thymosin α-1 group（7 cases）. During 1 mo after liver transplantation, according to the individual differences of patients, different doses and types of immunosuppressants including tacrolimus, mycophenolate and sirolimus were used. The combination group was additionally given Huaier granule and thymosin α-1 after 1 mo, and the other two groups were given Huaiergranule and thymosin α-1, respectively. The time of tumorrecurrence and the expression of Treg cells,IL-10 and TGF-β were observed. Each patients were followed for 24 mo.RESULTS： The disease-free survival was significantly longer in the combination group than in the other two groups（P 〈 0.05）. At the sixth month, the expression of Treg and IL-10 in the peripheral blood was significantly higher in the combination group than in the thymosin α-1 group（P 〈 0.05）, but there was no significant difference between the Huaiergranule group and combination group（P 〉 0.05）. At the twelfth month, the expression of Treg cells, IL-10, and TGF-β in the peripheral blood was significantly higher in the combination group than in the other two groups（P 〈 0.05）.CONCLUSION： Thymosin α-1 based antitumor therapy can obviously prolong liver tumor recurrence after transplantation.Regular monitoring of expression of Treg cells,IL-10 and TGF-β can be used as an auxiliary method for monitoring tumor recurrence after liver transplantation.