. Q8 O! K* D9 _2 {- H9 g& P 广州中山医科大学肿瘤中心的Pan等人[14],回顾性分析410例肝癌患者术后接受CIK治疗(204例)和不接受CIK治疗(206例)生存率的比较,发现肝癌切术后接受至少4个疗程的CIK免疫细胞治疗,总体生存率明显提高。接受8个疗程以上的CIK治疗组,较8个疗程以下的CIK治疗组疗效更佳。' r9 R4 M. z! J( N4 c; ]
8 r4 ]9 G1 i( ]0 y5 g$ F9 B- \ 广东中山大学Xu L等人[15]联合香港中文大学、美国Johns Hopkins大学,采用随机、对照研究,共同研究肝癌切除术后CIK免疫细胞治疗的疗效。200名肝癌切除术后患者随机分为两组,一组100例患者接受4个疗程的CIK治疗,另外100名患者作为对照组。结果显示:肝癌术后CIK治疗组中位肿瘤复发时间延长(P=0.01),但是总生存率(OS)和疾病无进展生存率(DFS)无统计学差异。治疗并发症在两组间无差别。结论[15]:4个疗程的CIK免疫细胞治疗是安全的,能有效延长肿瘤复发时间,预防肝癌复发,但是没有改善肝癌的总生存率和肿瘤无进展生存。 8 n( w/ `7 {0 J: @ ! @3 a* e! b* @; E5 J 天津医科大学肿瘤医院Hui等人[16]研究肝癌根治性切除术后输入自体CIK免疫细胞的疗效。127例肝癌根治性切除术后患者随机分为3组:41例患者给予CIK治疗3个疗程;43例患者给予CIK治疗6个疗程;另外43例患者无术后CIK治疗,作为对照组。结果显示[16]:CIK治疗组无肿瘤复发生存时间明显延长;术后输入3个疗程CIK和输入6个疗程CIK,无复发生存时间没有统计学差别。结论:肝癌切除术后给予CIK免疫细胞治疗,能预防肝癌转移和复发,但对患者的总体生存率没有影响。 3 @9 }- F- e( G; Z# e 0 o/ o+ ?! _, |% w: w2 D: c5 U+ ^ 作者对以上CIK治疗肝癌研究小结:# {2 `* t( V6 t$ B
1、肝细胞肝癌(HCC)输入CIK免疫细胞治疗后,绝大多数国内外医院发表的SCI文章,都提示CIK免疫细胞治疗能预防肝癌的复发,部分研究认为CIK治疗能提高肝癌患者的总生存率[7,12,13,14]。 # P; g$ d5 V) C/ W 2、无论是手术切除术后的肝癌患者,还是不能手术切除的患者,CIK治疗后都能获益,部分文献支持输入CIK治疗次数增加,疗效更明显[11,14]。 # Z4 q2 d* c7 _4 }7 T% h! ?' P 3、肝癌除外手术、肝动脉栓塞、损毁(射频、乙醇注射、冷冻等)治疗外,因对放、化疗不敏感,临床能使用的辅助治疗方法十分有限,而CIK治疗副作用低,目前是一种较为理想的肝癌辅助治疗方法。 + J. F+ I3 i2 K# e; j- b' P8 c8 P/ ^0 |0 D) a 参考文献: 1 v# u; D1 J! T8 f) {4 E& X- f% }' C7. Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.8 L+ e8 [9 E; z
9. Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000 Sep 2;356(9232):802-7." Z4 R" V3 G9 U: A- g
10. Olioso P, Giancola R, Di Riti M, Contento A, Accorsi P, Iacone A. Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial. Hematol Oncol. 2009 Sep;27(3):130-9. # W. a) [8 u: s& n7 r11. Cui J, Wang N, Zhao H, Jin H, Wang G, Niu C, Terunuma H, He H, Li W.Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma. Int J Cancer. 2014 Jan 15;134(2):342-51.% y7 n, ~/ V. _
12. Li X, Dai D, Song X, Liu J, Zhu L, Xu W. A meta-analysis of cytokine-induced killer cells therapy in combination with minimally invasive treatment for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2014 Oct;38(5):583-91.7 T4 q/ `, K, A3 t! E$ ^; Z
13. Yu X, Zhao H, Liu L, Cao S, Ren B, Zhang N, An X, Yu J, Li H, Ren X. A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma. J Clin Immunol. 2014 Feb;34(2):194-203. 5 f. e- i; H) y! r) d- T14. Pan K, Li YQ, Wang W, Xu L, Zhang YJ, Zheng HX, Zhao JJ, Qiu HJ, Weng DS, Li JJ, Wang QJ, Huang LX, He J, Chen SP, Ke ML, Wu PH, Chen MS, Li SP, Xia JC, Zeng YX.The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients. Ann Surg Oncol. 2013 Dec;20(13):4305-11. doi: 10.1245/s10434-013-3144-x. Epub 2013 Jul 27. 6 S5 _3 D3 S; F M* M15. Xu L, Wang J, Kim Y, Shuang ZY, Zhang YJ, Lao XM, Li YQ, Chen MS, Pawlik TM, Xia JC, Li SP, Lau WY. A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma. Oncoimmunology. 2015 Oct 12;5(3):e1083671. eCollection 2016. $ N- ]3 f0 l% f' X; v- l- h
16. Hui D, Qiang L, Jian W, Ti Z, Da-Lu K. A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma. Dig Liver Dis. 2009 Jan;41(1):36-41. ) y$ j5 p+ ]; b7 Z7 `2 S* I