TACE联合PMCT序贯自身肿瘤疫苗与免疫效应细胞治疗大肝癌临床观察

目的：评价经皮肝动脉化疗栓塞（transcatheter arterial，TACE）联合经皮冷循环微波凝固（percataneous micro—wave coaqulation therapy，PMCT）序贯人自体肝癌细胞溶胞产物荷栽树突状细胞（dendritic cells，DC）和细胞因子诱导杀伤（cytokine—induced killer，CIK）细胞、yST细胞治疗原发性大肝癌的临床疗效。方法：收集2008—01-01—2011—12-31徐州解放军第九七医院80例不能切除的原发性大肝癌患者随机分为研究组（过继性细胞免疫治疗）和对照组（TACE＋PMCT），每组各40例。对照组患者先行TACE，5～7d复查增强CT和彩超了解肿瘤碘油沉积和血供后再行PMCT；研究组TACE＋PMCT方法同对照组，PMCT后行免疫效应细胞（肝癌细胞溶胞产物荷载DC＋CIK细胞＋y6T细胞）治疗，采用静脉回输＋肝瘤体内注射。随访6～36个月，观察治疗前后肿瘤影像学资料（增强CT、彩超）、肝功能、AFP、免疫功能、生活质量、生存及并发症。结果：研究组和对照纽有效率分别为90％和85％，差畀无统计学意义，x2=0．457，P=0．737。研究组治疗后的CD4、CD4’／CD8’和NK细胞均明显高于治疗前、也明显高于对照组的治疗后，差异有统计学意义，P〈0．05。两组治疗后CD4^＋CD25^＋FOXP＋3／CD4^＋均明显低于治疗前，差异有统计学意义，P〈0．05。研究组和对照组治疗后AFP下降〉80％的分别为77．8％和67．5％，差异无统计学意义，x2=2．125，P=0．145。研究组的生存质量明显高于对照组，差异有统计学意义，P〈O．05。研究组的0．5、1和2年生存率分别为95％、80．0％和45％，对照组分别为90％、67．5％和30％，差异无统计学意义，P〈0．05。研究组和对照组中位生存期分别为21和17个月，差异有统计学意义，x^2=657．704，P=0．001。结论：肝动脉化疗栓塞联合冷循环微波凝固并序贯自身肿瘤疫苗和免疫细胞治疗大肝癌有效、安全，能改善患者的免疫功能、生活质量及中位生存，有可能延长患者的生存期。

TACE combined PMCT sequential own cancer vaccine and immunoeffector cells to treat large hepatocellular carcinoma clinical observation

OBJECTIVE：To evaluate the clinical value of transcatheter arterial chemoembolization （TACE） combined with ultrasonic guided water circulatory cooling percutaneous microwave coagulation therapy （PMCT） and sequential with dendritic ceils （DC） pulsed with autologous hepatoma ceil lysates and Cytokine-induced killer （CIK）ceIls and 73 T cells in treatment of large hepatocellular carcinoma （HCC）. METHODS：From 2008- 01- 01 to 2011-12--31, department of on cology the 97th Hospital of PLA,80 patients with unresectable large HCC were randomized into study group （TACE＋ PMCT＋ DC pulsed with autologous hepatoma cell lysates and CIK cells and 73 T cells n=40） and control group （TACE PMCT n=40）. Patients of control group were treated with TACE frist, after 5--7 days reexaminations such as con- trast-enhanced CT and Color Doppler ultrasound were taken to evaluate the information of Iodinated Oil sedimentation and blood supply then the patients were treated with PMCT. TACE and PMCT of study group was the same as control group. After PMCT the study group was treated with immunoeffector cells （DC loaded with hepatocellular carcinoma antigen and CIK cells and 73 T cells）, inclouding intravenous drip and tumor injection. The follow-up time ranged from 6 to 36 months,including contrast-enhanced CT and Color Doppler ultrasound, hepatic function and the AFP,immunological inde- xes and quality of life as well as the survival and complications. RESULTS： The response rate of the study group and con- trol group were 900/00 and 850/00 respectively,no significant differences was found between the two groups （x2 =0. 457 ,P= 0. 737）. CD4＋ and CD4＋/CD8＋ and NK cells in the treatment of the study group were significantly higher than thosebefore treatment and those after treatment in the control group（P〈0.05）. CD4 CD25＋ FOXP-i-3/CD4＋ of the two groups were significantly lower than those before treatment（P〈0.05）. AFP down more than 80 % of the study group and the control group were 77.8% and 67.5% respectively （X2 --2. 125,P=-0. 145）. Quality of living of the study group was higher of the control group （P（0.05）. The 0.5-,1-,2 years survival rates of the study group and the control group were 95%,80.0% ,45% and 90% ,67.5%,30% respectively （P〈0. 05）. The median survival of two groups were 21 months and 17 months respectively （x2--657. 704,P=-0. 001）. CONCLUSIONS： TACE combined with PMCT and sequential DC pulsed with autologous hepatoma cell lysates and CIK cells and 78 T cells is a safe and effectiveness method in the treatment of HCC,improving quality of living and immunological function and the median survival. It is possible to prolong the survival of patients.