CIK细胞输注联合TACE治疗延缓原发性肝癌患者门静脉癌栓的形成

doi:10.3969/j.issn.1672-5069.2016.03.016

摘要/Abstract

摘要： 目的探讨细胞因子诱导的杀伤细胞（CIK）输注联合经动脉插管化疗栓塞术（TACE）治疗原发性肝癌患者延缓门静脉癌栓形成的可能性。方法选择2010年1月～2014年12月我院收治的原发性肝癌患者44例，22例接受TACE联合CIK细胞输注治疗，另22例只接受TACE治疗。采用Ficoll两步分离法分离外周血单个核细胞，经IFN-γ、抗CD3单克隆抗体和 IL-2诱导，使用流式细胞仪检测细胞CD抗原表达鉴定CIK细胞培养成功，常规行TACE治疗，在TACE治疗半月后输注CIK细胞悬液3次，细胞总数为1.0×109。治疗前后行腹部CT检查，确定门静脉栓子形成情况。结果治疗后1 m、3 m和6 m，联合组患者门静脉癌栓发生率分别为4.5%、13.6%和27.2%，而TACE组则分别为9.0%、45.5%和63.6%（P<0.05）；在治疗3月时，联合组肿瘤大小为（4.77±1.27）cm，显著低于TACE组[（5.54±1.14）cm,P＜0.05]；在治疗3月时，联合组血清甲胎蛋白水平为(83.14±31.91) ng/ml，也显著低于TACE组[(139.24±98.76) ng/ml，P＜0.05]；两组肺部、颅脑和骨骼等远处转移发生率无显著性差异（P>0.05）。结论 CIK细胞输注联合TACE可明显减缓原发性肝癌患者门静脉栓子形成的时间，改善肝功能，同时能有效控制肿瘤的生长及扩散。

关键词: 原发性肝癌, 门静脉癌栓, 细胞因子诱导的杀伤细胞, 过继免疫疗法, 经动脉插管化疗栓塞术

Abstract: Objective To investigate the effects of cytokine induced killer cells( CIK) combined with transcatheter arterial chemoembolization（TACE） for patients with primary liver cancer（PLC）. Methods A total of 44 patients with PLC were enrolled in 105th hospital between January 2010 and December 2014. 22 patients received combination CIK infusion and TACE，and 22 were treated with TACE alone. The peripheral blood mononuclear cells were obtained by Ficoll separation, and the CIKs were induced by with interferon-γ, anti-CD3 monoclonal antibodies and interleukin-2 incubation. The cells were determined by FACs detection. About 1.0×109 of CIKs were transfused after routine TACE，and abdominal CT scan was done for assessment of occurrence of portal vein tumor thrombus(PVTT). Results The incidence of PVTT in CIK and TACE combination group 1 m, 3 m and 6 m after the discontinuation of the therapy were 4.5%,13.6% and 27.2%，while those in TACE group were 9.0%, 45.5% and 63.6%, respectively（P<0.05）；the size of tumor mass in combination group at 3 m was （4.77±1.27）cm，much smaller than[（5.54±1.14）cm,P＜0.05] in TACE-treated patients；serum alpha-fetoprotein in combination group at 3 m was（83.14±31.91） ng/ml，much lower than[(139.24±98.76) ng/ml，P＜0.05] in TACE group；the remote metastasis, such as lungs, brain, bone, etc, in both groups were not significantly different（P>0.05）. Conclusion Combination of CIK and TACE treatment can prevent patients with PLC developing PVTT occurrence, and maybe improve the life of quality of patients with PLC.

Key words: Primary liver cancer, Cytokine-induced killer cells, Transcatheter arterial chemoembolization, Adoptive immunotherapy, Portal vein tumor thrombus

宋海燕，刘波，张骏飞，董静，郭远，刘利伟，陈从新. CIK细胞输注联合TACE治疗延缓原发性肝癌患者门静脉癌栓的形成[J]. 实用肝脏病杂志, 2016, 19(3): 318-321.

Song Haiyan,Liu Bo,Zhang Junfei,et al.. Effects of cytokine-induced killer cell infusion after transcatheter arterial chemoembolization in treatment of patients with primary liver cancer on preventing portal vein tumor thrombus[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(3): 318-321.

参考文献

[1] Jemal A, Siegel R, Xu J, et al. Cancer statistics,2010. CA Cancer J Clin, 2010,60(5): 277-300.
[2] 施明,王福生,张冰,等.自体CIK细胞治疗肝癌的安全性和有效性评价.解放军医学杂志,2004,29(4):333-335.
[3] 赵明、吴沛宏、曾益新,等.经肝动脉栓塞化疗序贯联合射频消融和细胞因子诱导的杀伤细胞治疗肝细胞癌的随机研究.中华医学杂志，2006，86（26）：1823-1828.
[4] 张艳梅,崔红利,颜綦先,等.CIK细胞疗法联合TACE治疗原发性肝癌患者临床疗效观察.实用肝脏病杂志，2015，18（6）：647-650.
[5] 中华人民共和国卫生部[卫办医政改（2011）121号].原发性肝癌诊疗规范（2011年版）摘要.中华肝脏病杂志,2012,20:419-426.
[6] 李慧芬,李晓玲,黄玉玲,等.CIK治疗11例中晚期肾癌的预后分析.肿瘤基础与临床,2009,22(1):55-57.
[7] Marin V，Pizzitola I，Agostoni V，et al．Cytokine-induced killer cells for cell therapy of acute myeloid leukemia ：Improvement to their immune activity by expression of CD33-specific chimeric receptors．Haematologica,2010,95(12): 2144-2152.
[8] 张素青,施玲燕,刘继斌,等.CIK细胞治疗晚期肝癌的临床观察.肿瘤基础与临床,2009,22（6）:505-507.
[9] Niu Q, Wang W，Li Y，et al．Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies．Int Immunopharmacol,2011,11(4):449-456.
[10] Li JJ, Gu MF, Pan K, et al．Autologous cytokine-induced killer cell transfusion in combination with gemcitabine plus cisplatin regimen chemotherapy for metastatic nasopharyngeal carcinoma．J Immunother,2012,35(2):189-195.
[11] Sun K, Wang L, Zhang YY. Dendritic cell as therapeutic vaccines against tumors and its role in therapy for hepatocellular carcinoma. Cell Mol Immunol, 2006,3(3):197-203.
[12] 王家祥,郑树,刘秋亮. 不同来源CIK细胞的体外扩增和杀伤活性的比较.第四军医大学学报,2005,26(7):616-618.
[13] 王洁,牟青杰,王占聚.脐血来源CIK细胞的诱导及检测.疑难病杂志,2010,9(1):17- 18.
[14] Nakashima T. Pathology of hepatocellar carcinoma: tumor thrombus of the portal vein. Acta Hepathologica Japonica,1984,25:120-126.
[15] 吴孟超,陈汉,沈锋. 原发性肝癌的外科治疗-附5524例报告.中华外科杂志,2001,39:25-28.
[16] Chau CY, Lui WY, Wu CW. Spectrum and significance of microscopic vascular invasion in hepatocellular. Surg Oncol Clin Nam,2003,12:25-34.
[17] 吴照宇.中、晚期肝癌介入治疗预后的影响因素分析.实用肝脏病杂志,2015,18（4）：427-429.
[18] 程树群,吴孟超,程红岩.原发性肝癌门静脉癌栓生长特征的研究.中国现代普通外科进展,2003,6:103-105.
[19] European Association For The Study of the Liver, European Organisation for Research and Treatment Of Cancer. EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. J Hepatol,2012,56(4): 908-943.
[20] Bruix J, Sherman M. Management of hepatocellular carcinoma: an update, Hepatology, 2011,53(3):1020-1022.
[21] Pinter M, Hucke F, Graziadei I, et al. Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. Radiology, 2012, 263, 2: 590-599.