目的 观察肝动脉栓塞化疗(transcatheter arterial chemoembolization,TACE)联合过继T细胞免疫疗法对中晚期肝癌的近期疗效,以及对外周血T淋巴细胞亚群及Treg细胞计数的影响。方法 回顾分析114例中晚期原发性肝癌患者实行TACE联合过继T细胞疗法(研究组)或单一TACE治疗(对照组)的资料。研究组(56例)全部经过TACE术且术后第2天接受过继T细胞回输;对照组(58例)仅接受TACE治疗。治疗为每4周一次,最多不超过3次,观察疗程为2年。观察无进展生存期(progress free survival, PFS)和总生存期(overall survival, OS),以及治疗前后相同时间点测定T淋巴细胞亚群、Treg细胞以及AFP计数变化。结果 研究组与对照组的近期疗效及AFP下降率比较,无统计学差异。研究组治疗后6个月、1年、2年的无进展生存率分别是71.4%、23.2%、5.4%;对照组分别是65.5%、31.0%、3.4%。两组中位疾病进展时间分别是8个月(95%CI,8-11个月)和5个月(95%CI,6-9个月)。研究组治疗后6个月、1年、2年的总生存率分别是89.2%、71.4%、60.7%,对照组分别是70.6%、41.4%、17.2%。两组中位生存期分别是18个月(95% CI,16-20个月)和11个月(95% CI,9-13个月)。研究组CD4⁺细胞比率由治疗前(51.27±4.85)%升至(54.51±5.03)%,CD8⁺以及Treg细胞计数分别由(40.87±3.26)%和(6.36±0.98)%下降至(37.24±3.56)%和(3.89±0.31)%,CD4⁺/CD8⁺比值增大(P<0.05);对照组治疗后与治疗前相比无统计学差异。结论 中晚期肝癌患者TACE术后联合过继T细胞疗法可提高无进展生存期和总生存期,并能提高免疫能力,增强机体的抗肿瘤效应,有可能降低中晚期肝癌患者的复发率和转移率。

Objective To study the different affects of TACE alone and TACE combined with adoptive T lymphocytes on the peripheral T lymphocyte subsets and Treg cells for advanced hepatocellular carcinoma(HCC). Methods 114 patients with advanced stage HCC were recruited, 56 patients were treated with TACE followed by adoptive T lymphocytes treatment,and 58 patients were treated with TACE only as a control group. Each patient was treated once a month, successive 3 times were a course of treatment. The duration of the observation was 2 years. The progress free survival(PFS) and overall survival(OS), serum levels of AFP, T lymphocyte sunsets and Treg cells in peripheral blood of advanced HCC patients were found out before and after the treatments. Results The short-term responses in the 2 groups were similar. There was also no significant difference in the reduction rates of AFP between these two groups. The 6 months, 1 year, and 2 years PFS rates were 71.4%, 23.2%, 5.4% in combination group, and 65.5%, 31.0%, 3.4% in control group. The median TTP (time to progression)was 8 months (95% confidence interval CI,8-11 months) for combination group and 5 months(95% confidence interval CI,6- 9 months) for control group. The proportion of 6 months, 1 year, and 2 years OS were 89.2%, 71.4% and 60.7% in combination group, while in control group they were 70.6%, 41.4%, 17.2%(P<0.05) , respectively. The median survival time was 18 months(95% CI,16-20 months)in combination group and 11 months(95% CI,9-13 months)in control group. In the study group, the percentage of CD4⁺ increased from(51.27?4.85)% to(54.51?5.03)% (P<0.05), CD8⁺ and Treg cells decreased from (40.87?3.26)%,(6.36?0.98)% to (37.24?3.56)%,(3.89?0.31)% (P<0.05), respectively. The rates of CD4⁺/CD8⁺ increased greatly(P<0.05). There was no significant difference compared between before and after treatment in the control group. Conclusions Adjuvant immunotherapy with adoptive T lymphocytes may prolong the PFS and OS in advanced HCC patients, and there is a statistically significant difference. It can improve immunological status as well as the efficacy of TACE in these patients. It may also play an important role in reducing the recurrence and metastases in HCC patients.