Fang S J, Zheng L Y, Zhao Z W, Fan X X, Xu M, Ji J S
Department of Interventional Radiology, Lishui Hospital of Zhejiang University, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Municipal Central Hospital, Lishui 323000, China.
Zhonghua Yi Xue Za Zhi. 2017 Jul 4;97(25):1942-1946. doi: 10.3760/cma.j.issn.0376-2491.2017.25.005.
To investigate the effect of transcatheter arterial chemoembolization(TACE)combined with thymosin alpha1(Tα1)on the autophagy of immune cells from advanced hepatocellular carcinoma. A total of 30 patients with advanced liver cancer enrolled in Lishui Central Hospital from September 2015 to June 2016 were collected in this study. The average age of patients was 16-75(56±12) years. All patients were treated with TACE after enrolled in hospital in a week. Patients were divided into TACE group and TACE+ Tα1 treatment group(15 cases in each group). Patients in TACE group received a conventional treatment, without any immunotherapy, while the TACE+ Tα1 treatment group accepted TACE following a subcutaneously injection of 1.6 mg Tα1 twice a week for 4 weeks. Flow cytometry was used to detect the T cell subsets in two groups both before and after TACE treatment for 1, 4 weeks and at 3 months follow-up. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The expression of Beclin-1, LC3 protein and mRNA were detected by Western blot (WB) and PCR respectively. There was no statistical difference of the percentage of CD3(+) , CD4(+) , CD8(+) T cell subsets and Beclin-1, LC3 protein and mRNA expression between the two groups before TACE treatment (>0.05). The percentage of CD3(+) , CD4(+) , CD8(+) T cell subsets in TACE+ Tα1 group at 1 week post-TACE treatment (58.45%±16.34%, 38.33%±15.16%, 27.31%±12.54%), at 4 weeks post-TACE treatment (62.38%±18.62%, 43.19%±13.86%, 29.54%±10.33%) and 3 months follow-up (64.15%±13.76%, 41.28%±14.65%, 29.38%±15.65%) were statistically higher than those in TACE group at 1 week post-TACE treatment (53.71%±11.17%, 32.12%±10.53%, 24.45%±13.72%) at 4 weeks post-TACE treatment (52.12%±14.26%, 31.16%±15.43%, 23.39%±15.33%) and 3 months follow-up (54.28%±13.15%, 32.17%±14.98%, 24.34%±14.12%) (<0.05). The Beclin-1, LC3 protein and mRNA expression in TACE+ Tα1 group at 1 week post-TACE treatment (protein: 0.57±0.08, 2.26±0.36, mRNA: 0.62±0.11, 2.69±0.27), at 4 weeks post-TACE treatment (protein: 0.66±0.09, 3.11±0.45, mRNA: 0.78±0.13, 3.43±0.61) were higher than those in TACE group at 1 week post-TACE treatment (protein: 0.45±0.16, 1.43±0.30, mRNA: 0.52±0.15, 1.15±0.37), at 4 weeks post-TACE treatment (protein: 0.51±0.13, 1.81±0.35, mRNA: 0.56±0.10, 1.98±0.41) ( <0.05). But there was no statistically significant difference in the expression of Beclin-1 and LC3 in two groups at 3 months follow-up (>0.05). TACE combined with Tα1 significantly increase the level of autophagy in the immune cells of patients with advanced primary hepatocellular carcinoma.
探讨经动脉化疗栓塞术（TACE）联合胸腺肽α1（Tα1）对晚期肝细胞癌患者免疫细胞自噬的影响。本研究收集了2015年9月至2016年6月在丽水市中心医院就诊的30例晚期肝癌患者。患者平均年龄为16 - 75（56±12）岁。所有患者入院一周后均接受TACE治疗。患者分为TACE组和TACE + Tα1治疗组（每组15例）。TACE组患者接受常规治疗，未进行任何免疫治疗，而TACE + Tα1治疗组在TACE治疗的同时，每周皮下注射1.6 mg Tα1，共4周。采用流式细胞术检测两组患者在TACE治疗前、治疗后1周、4周及随访3个月时的T细胞亚群。通过密度梯度离心法分离外周血单个核细胞（PBMC）。分别采用蛋白质印迹法（WB）和聚合酶链反应（PCR）检测Beclin-1、LC3蛋白及mRNA的表达。TACE治疗前，两组患者CD3(+)、CD4(+)、CD8(+) T细胞亚群百分比及Beclin-1、LC3蛋白和mRNA表达差异均无统计学意义（>0.05）。TACE + Tα1组患者在TACE治疗后1周（58.45%±16.34%、38.33%±15.16%、27.31%±12.54%）、4周（62.38%±18.62%、43.19%±13.86%、29.54%±10.33%）及随访3个月时（64.15%±13.76%、41.28%±14.65%、29.38%±15.65%）的CD3(+)、CD4(+)、CD8(+) T细胞亚群百分比均显著高于TACE组在TACE治疗后1周（53.71%±11.17%、32.12%±10.53%、24.45%±13.72%）、4周（52.12%±14.26%、31.16%±15.43%、23.39%±15.33%）及随访3个月时（54.28%±13.15%、32.17%±14.98%、24.34%±14.12%）（<0.05）。TACE + Tα1组患者在TACE治疗后1周（蛋白：0.57±0.08、2.26±0.36，mRNA：0.62±0.11、2.69±0.27）、4周（蛋白：0.66±0.09、3.11±0.45，mRNA：0.78±0.13、3.43±0.61）时的Beclin-1、LC3蛋白及mRNA表达均高于TACE组在TACE治疗后1周（蛋白：0.45±0.16、1.43±0.30，mRNA：0.52±0.15、1.15±0.37）、4周（蛋白：0.51±0.13、1.81±0.35，mRNA：0.56±0.10、1.98±0.41）时的表达（<0.05）。但两组患者在随访第3个月时Beclin-1和LC3的表达差异无统计学意义（>0.05）。TACE联合Tα1可显著提高晚期原发性肝癌患者免疫细胞的自噬水平。
