摘要
背景与目的树突细胞(Dendriticcells,DC)是目前发现的功能最强大的肿瘤抗原专职免疫递呈细胞,DC疫苗是目前最具临床应用潜能的治疗性疫苗。肿瘤细胞凋亡小体被DC的MHC-I分子提呈并诱导的特异性CTL免疫反应抗癌作用显著。本研究探讨了DC负载凋亡癌细胞抗原后诱导的免疫应答联合β-榄香烯对小鼠胰腺癌治疗作用。方法制备C57BL/6小鼠骨髓源性DC并鉴定,负载肿瘤抗原后制备成疫苗。分别观察DC诱导的CTL和β-榄香烯对胰腺癌细胞的杀伤作用。体内观察DC疫苗联合β-榄香烯对小鼠胰腺癌的抑制作用。结果经电镜及流式细胞鉴定可获得典型的具有抗原加工及递呈作用的DC,利用TNF-α可使成熟的树突状细胞比例增加,MHC-Ⅱ、CD83、CD86等表面分子的表达较单纯DC组显著增强。负载凋亡抗原后DC诱导的特异性CTL体外对胰腺癌细胞有显著杀伤作用,效靶比30∶1时,诱导的CTL对胰腺癌细胞抑制率达93%。β-榄香烯对癌细胞增殖抑制明显,DC疫苗与β-榄香烯联合治疗可明显抑制荷瘤小鼠肿瘤的生长,使其生存期延长,联合治疗组生存期为49.4天,与单纯β-榄香烯组(24.8天)、DC疫苗(38.5天)、DC组(20.7天)及对照组(17.5天)相比有显著差异(P<0.05)。结论经凋亡肿瘤细胞致敏的DC回输荷瘤小鼠可激发宿主针对特异肿瘤的Th1及CTL免疫应答,以DC介导的免疫反应联合中药的治疗方法可成为抗肿瘤的崭新且有效手段。
Background and purpose： Dendritic cells（BM-DCs） have recently been found to be the most powerful and specific tumor antigen presenting cells. DC vaccine is one of the treatment options that is being deeply investigated and might have potential for clinical application. Specific CTL immune responses to apoptotic antigen of tumor cell, which is induced and presented by DC with MHC-Ⅰ molecule, show stronger anti-tumor effect. The purpose of this study is to explore the treatment of β-elemene combined with immune responses induced by bone marrow-derived dendritic cells after acquiring apoptotic antigen for pancreatic carcinoma. Methods： The C57BL/6 murine DCs were pulsed with apoptotic tumor cell antigen. The immunotherapeutic effects induced by DE vaccines combined with β-elemene on murine pancreatic carcinoma were assessed. CTL immune response and proliferating inhibition were assessed in vitro; survival period and tumor regression were observed in vivo. Results： Antigen presenting mature DEs＇with highly expressed surface molecules MHC-Ⅱ 、CD83、CD86 were induced by TNF-α. CTL response induced by DC after acquiring apoptotic antigen show strong cytotoxic activity against pancreatic cancer cells. Proliferation inhibition rate is about 93% when effect/target ratio is 30： 1, β-elemene could efficiently inhibit the proliferation of cancer cells in vitro. The tumor size regressed markedly and the survival period was markedly prolonged for mice treated by DC vaccines combined with β-elemene group, compared to the other four groups （P 〈0.05）. Conclusions： CTL and Th1 immune response stimulated by DC vaccines pulsed with apoptotic antigen have very strong cytolytic activity against pancreatic cancer cells. The dentric cell vaccines combined with elemene may be one of the new methods that may have an effective immune and chemotherapeutic function against tumor cells implanted in mice.
出处
《中国癌症杂志》
CAS
CSCD
2007年第1期50-53,共4页
China Oncology
基金
辽宁省科技厅自然基金资助项目(No.20042138)。
关键词
树突状细胞
Β-榄香烯
胰腺癌
免疫治疗
小鼠
dendritic cell
β-elemene
pancreatic carcinoma
immune treatment
mice
