DC-CIK细胞免疫疗法在肝细胞癌治疗中的应用进展
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摘要
肝癌是临床上常见的恶性肿瘤,病死率高,大部分患者患病时已失去最佳手术治疗时机。目前主要的保守治疗方法有超声引导下肿瘤射频消融、肝动脉栓塞疗法、生物免疫治疗以及分子靶向治疗等。因肝癌是一种免疫相关疾病,为探索有效的细胞免疫治疗方案,提高患者生存率及生活质量,该文就树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)免疫疗法在肝癌治疗中的应用进行了综述。
Hepatocellular carcinoma(HCC) is a common malignant tumor with high mortality. Most patients lose the best opportunity for surgical treatment when diagnosed. The main conservative therapies are ultrasound-guided radiofrequency ablation, hepatic artery embolization therapy, bio-immunotherapy and molecular targeted therapy. Because hepatocellular carcinoma is an immune-related disease, in order to explore effective cellular immunotherapy regimen and improve the survival rate and quality of life of patients, this article reviews the application of dendritic cells and cytokine-induced killer(DC-CIK) immunotherapy in hepatocellular carcinoma.
Hepatocellular carcinoma(HCC) is a common malignant tumor with high mortality. Most patients lose the best opportunity for surgical treatment when diagnosed. The main conservative therapies are ultrasound-guided radiofrequency ablation, hepatic artery embolization therapy, bio-immunotherapy and molecular targeted therapy. Because hepatocellular carcinoma is an immune-related disease, in order to explore effective cellular immunotherapy regimen and improve the survival rate and quality of life of patients, this article reviews the application of dendritic cells and cytokine-induced killer(DC-CIK) immunotherapy in hepatocellular carcinoma.
引文
[1]NISHIKAWA H,INUZUKA T,TAKEDA H,et al.Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma[J].BMC Gastroenterol,2011,11:143.
[2]单婵婵,石亮荣,丁美钱,等.肿瘤射频消融裂解物负载的DC-CIK细胞体外抗肿瘤活性实验研究[J].国际肿瘤学杂志,2014,41(6):471-475.
[3]赵建夫,徐萌.CIK细胞免疫联合TACE微创治疗原发性肝癌的研究进展[J].中国病理生理杂志,2015,31(7):1334-1339.
[4]李娜,李敏,冯珉.CIK细胞疗法联合肝动脉化学治疗栓塞术治疗原发性肝癌的临床探究[J].国消化病杂志,2016,36(6):369-371.
[5]GONZáLEZ-CARMONA M A,M?RTEN A,HOFFMANNP,et al.Patient-derived dendritic cells transduced with an afetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells[J].Liver Int,2006,26(3):369-379.
[6]SHAN C C,SHI L R,DING M Q,et al.Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response[J].Oncol Lett,2015,9(4):1549-1556.
[7]SHI B,SUN A,ZHANG X.Influence of different ex vivo cell culture methods on the proliferation and anti-tumor activity of cytokine-induced killer cells from gastric cancer patients[J].Onco Targets Ther,2018,11:2657-2672.
[8]郭伟伟,刘莉,吴德华.DC-CIK细胞免疫治疗联合TACE术治疗原发性肝癌[J].南方医科大学学报,2014,34(5):674-678.
[9]AHN S,CHO A,KIM E K,et al.Favorable long-term oncologic outcomes of hepatocellular carcinoma following laparoscopic liver resection[J].J Laparoendosc Adv Surg Tech A,2016,26(6):447-452.
[10]马洪波,黄涛,韩风,等.DC-CIK细胞联合手术治疗原发性肝癌的临床研究[J].重庆医科大学学报,2012,37:980-983.
[11]石磊,于法涛,谢智慧.CIK细胞联合介入疗法治疗早期肝癌效果研究[J].中国医学前沿杂志(电子版),2016,8(9):137-140.
[12]董安楠,李旺,吴方明,等.细胞因子诱导杀伤细胞免疫联合微创介入治疗早期肝癌的长期临床疗效观察[J].中华医学杂志,2015,95(33):2668-2672.
[13]贾咏存,海金富,朴文花.DC-CIK细胞免疫疗法对原发性肝癌患者免疫功能的影响[J].宁夏医科大学学报,2016,38(2):144-146.
[14]李金瑞,钟鑫平.射频消融联合DC‐CIK治疗中晚期肝细胞癌的疗效评价[J].检验医学与临床,2015,12(19):2830-2833.
[15]LEE J H,LEE J H,LIM Y S,et al.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J].Gastroenterology,2015,148(7):1383-1391.
[16]LEE J H,LEE J H,LIM Y S,et al.Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma:an extended 5-year followup[J].Cancer Immunol,Immunother,2018.doi:10.1007/s00262-018-2247-4.[Epub ahead of print]
[17]CHEN C,MA Y H,ZHANG Y T,et al.Effect of dendritic cell-based immunotherapy on hepatocellular carcinoma:Asystematic review and meta-analysis[J].Cytotherapy,2018,20(8):975-989.
[18]高会霞.同步放化疗联合DC-CIK治疗局部晚期非小细胞肺癌的临床疗效分析[J].临床肺科杂志,2018,23(9):1596-1600.
[19]焦兰,陈芬,江千秋,等.DG-DIK联合靶向治疗及化疗在局部晚期乳腺癌新辅助治疗中的临床疗效分析[J].中国现代医学杂志,2015,25(36):21-25.
[20]刘庆,杨华夏,刘志为,等.DC-CIK联合化疗对晚期结直肠癌患者免疫功能及B7-H4蛋白表达的影响[J].临床和实验医学杂志,2017,16(9):898-901.
[21]CAI J B,SHI G M,DONG Z R,et al.Ubiquitin-specific protease 7 accelerates p14(ARF)degradation by deubiquitinating thyroid hormone receptor-interacting protein 12and promotes hepatocellular carcino-ma progression[J].Hepatology,2015,61(5):1603-1614.
[22]XIE N,CAI J B,ZHANG L,et al.Upregulation of B7-H4promotes tumor progression of intrahepatic cholangiocarcinoma[J].Cell Death and Disease,2017,8(12):3205.
[23]QIAN Y,HONG B,SHEN L,et al.B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells[J].Cell Tissue Res,2013,353(1):139-151.
[24]何涛,胡洪,谢楠,等.新型共刺激分子B7-H4表达抑制对人肝癌细胞增殖和凋亡的影响[J].山东医药,2018,58(29):33-36.
[25]陈晓敏,郭俊明,乐东海,等.上皮-间质转化:肿瘤转移的重要调控机制[J].中国细胞生物学学报,2013,35(9):1367-1375.
[26]丁碧莎,孙月娟,王海燕.DC-CIK联合化疗治疗非小细胞肺癌的研究进展[J].中国免疫学杂志,2016,32(6):916-919.
[27]WEN Y Y,HU X S.Anti-tumor activity of dendritic cellcytokine induced killer cells(DC-CIKs)sensitized to HER2against HER positive breast cancer cells[J].Genet Mol Res,2016,15(2):1-8.
[2]单婵婵,石亮荣,丁美钱,等.肿瘤射频消融裂解物负载的DC-CIK细胞体外抗肿瘤活性实验研究[J].国际肿瘤学杂志,2014,41(6):471-475.
[3]赵建夫,徐萌.CIK细胞免疫联合TACE微创治疗原发性肝癌的研究进展[J].中国病理生理杂志,2015,31(7):1334-1339.
[4]李娜,李敏,冯珉.CIK细胞疗法联合肝动脉化学治疗栓塞术治疗原发性肝癌的临床探究[J].国消化病杂志,2016,36(6):369-371.
[5]GONZáLEZ-CARMONA M A,M?RTEN A,HOFFMANNP,et al.Patient-derived dendritic cells transduced with an afetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells[J].Liver Int,2006,26(3):369-379.
[6]SHAN C C,SHI L R,DING M Q,et al.Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response[J].Oncol Lett,2015,9(4):1549-1556.
[7]SHI B,SUN A,ZHANG X.Influence of different ex vivo cell culture methods on the proliferation and anti-tumor activity of cytokine-induced killer cells from gastric cancer patients[J].Onco Targets Ther,2018,11:2657-2672.
[8]郭伟伟,刘莉,吴德华.DC-CIK细胞免疫治疗联合TACE术治疗原发性肝癌[J].南方医科大学学报,2014,34(5):674-678.
[9]AHN S,CHO A,KIM E K,et al.Favorable long-term oncologic outcomes of hepatocellular carcinoma following laparoscopic liver resection[J].J Laparoendosc Adv Surg Tech A,2016,26(6):447-452.
[10]马洪波,黄涛,韩风,等.DC-CIK细胞联合手术治疗原发性肝癌的临床研究[J].重庆医科大学学报,2012,37:980-983.
[11]石磊,于法涛,谢智慧.CIK细胞联合介入疗法治疗早期肝癌效果研究[J].中国医学前沿杂志(电子版),2016,8(9):137-140.
[12]董安楠,李旺,吴方明,等.细胞因子诱导杀伤细胞免疫联合微创介入治疗早期肝癌的长期临床疗效观察[J].中华医学杂志,2015,95(33):2668-2672.
[13]贾咏存,海金富,朴文花.DC-CIK细胞免疫疗法对原发性肝癌患者免疫功能的影响[J].宁夏医科大学学报,2016,38(2):144-146.
[14]李金瑞,钟鑫平.射频消融联合DC‐CIK治疗中晚期肝细胞癌的疗效评价[J].检验医学与临床,2015,12(19):2830-2833.
[15]LEE J H,LEE J H,LIM Y S,et al.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J].Gastroenterology,2015,148(7):1383-1391.
[16]LEE J H,LEE J H,LIM Y S,et al.Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma:an extended 5-year followup[J].Cancer Immunol,Immunother,2018.doi:10.1007/s00262-018-2247-4.[Epub ahead of print]
[17]CHEN C,MA Y H,ZHANG Y T,et al.Effect of dendritic cell-based immunotherapy on hepatocellular carcinoma:Asystematic review and meta-analysis[J].Cytotherapy,2018,20(8):975-989.
[18]高会霞.同步放化疗联合DC-CIK治疗局部晚期非小细胞肺癌的临床疗效分析[J].临床肺科杂志,2018,23(9):1596-1600.
[19]焦兰,陈芬,江千秋,等.DG-DIK联合靶向治疗及化疗在局部晚期乳腺癌新辅助治疗中的临床疗效分析[J].中国现代医学杂志,2015,25(36):21-25.
[20]刘庆,杨华夏,刘志为,等.DC-CIK联合化疗对晚期结直肠癌患者免疫功能及B7-H4蛋白表达的影响[J].临床和实验医学杂志,2017,16(9):898-901.
[21]CAI J B,SHI G M,DONG Z R,et al.Ubiquitin-specific protease 7 accelerates p14(ARF)degradation by deubiquitinating thyroid hormone receptor-interacting protein 12and promotes hepatocellular carcino-ma progression[J].Hepatology,2015,61(5):1603-1614.
[22]XIE N,CAI J B,ZHANG L,et al.Upregulation of B7-H4promotes tumor progression of intrahepatic cholangiocarcinoma[J].Cell Death and Disease,2017,8(12):3205.
[23]QIAN Y,HONG B,SHEN L,et al.B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells[J].Cell Tissue Res,2013,353(1):139-151.
[24]何涛,胡洪,谢楠,等.新型共刺激分子B7-H4表达抑制对人肝癌细胞增殖和凋亡的影响[J].山东医药,2018,58(29):33-36.
[25]陈晓敏,郭俊明,乐东海,等.上皮-间质转化:肿瘤转移的重要调控机制[J].中国细胞生物学学报,2013,35(9):1367-1375.
[26]丁碧莎,孙月娟,王海燕.DC-CIK联合化疗治疗非小细胞肺癌的研究进展[J].中国免疫学杂志,2016,32(6):916-919.
[27]WEN Y Y,HU X S.Anti-tumor activity of dendritic cellcytokine induced killer cells(DC-CIKs)sensitized to HER2against HER positive breast cancer cells[J].Genet Mol Res,2016,15(2):1-8.