CAJ | 학술논문

目的探讨含未甲基化“胞嘧啶-磷酸二酯键-鸟嘌呤(CpG)基序”的寡脱氧核糖核苷酸(CpG ODN)联合肿瘤表面抗原CA125共致敏树突状细胞(DC)对裸鼠人卵巢癌移植瘤生长的免疫抑制作用.方法自人外周血分离培养DC,流式细胞术鉴定DC表型特征;应用CpG ODN2006联合CA125体外冲击致敏DC,并与T淋巴细胞共培养获得细胞毒性T淋巴细胞(CTL).建立人OVCAR3卵巢癌荷瘤裸鼠模型,CTL经皮下注射免疫荷瘤裸鼠,绘制移植瘤生长曲线,通过计算抑瘤率、细胞凋亡率评估其对裸鼠人OVCAR3卵巢癌移植瘤的免疫抑制作用.结果分离培养DC低水平表达CD83、CD86,符合未成熟DC表型特征;联合致敏DC与T淋巴细胞共培养后获得CTL,经皮下免疫治疗,肿瘤出现延迟生长,抑瘤率达50.71％,抑瘤效果优于单纯CpG ODN致敏组和单纯CA125致敏组,差异有统计学意义(P＜0.05).联合致敏组和单纯CpG ODN致敏组肿瘤细胞凋亡率分别为(29.6±3.0)％和(21.8±2.7)％,均显著高于未致敏组和CA125致敏组(P＜0.05).结论 CpGODN联合CA125共致敏DC体外活化的CTL可有效抑制卵巢癌移植瘤生长,促进瘤细胞凋亡.
목적 탐토함미갑기화“포밀정-린산이지건-조표령(CpG)기서”적과탈양핵당핵감산(CpG ODN)연합종류표면항원CA125공치민수돌상세포(DC)대라서인란소암이식류생장적면역억제작용.방법 자인외주혈분리배양DC,류식세포술감정DC표형특정;응용CpG ODN2006연합CA125체외충격치민DC,병여T림파세포공배양획득세포독성T림파세포(CTL).건립인OVCAR3란소암하류라서모형,CTL경피하주사면역하류라서,회제이식류생장곡선,통과계산억류솔、세포조망솔평고기대라서인OVCAR3란소암이식류적면역억제작용.결과 분리배양DC저수평표체CD83、CD86,부합미성숙DC표형특정;연합치민DC여T림파세포공배양후획득CTL,경피하면역치료,종류출현연지생장,억류솔체50.71％,억류효과우우단순CpG ODN치민조화단순CA125치민조,차이유통계학의의(P＜0.05).연합치민조화단순CpG ODN치민조종류세포조망솔분별위(29.6±3.0)％화(21.8±2.7)％,균현저고우미치민조화CA125치민조(P＜0.05).결론 CpGODN연합CA125공치민DC체외활화적CTL가유효억제란소암이식류생장,촉진류세포조망.
Objective To explore the immunosuppressive action of dendritic cells (DC) sensitized by oligodeoxynucleotides containing " un-methylated cytimidine-phosphodiester bond-guanylic acid" motif (CpG ODN) and CA125 on human ovarian carcinoma xenografts in nude mice.Methods Human peripheral blood-derived dendritic cells were isolated and identified by flow cytometry.The DC sensitized by CpG ODN and CA125 were then co-cultured with T cells and finally cytotoxic T lymphocytes (CTL) were induced.Nude mice bearing OVCAR3 transplanted tumor were immunized with induced CTL by subcutaneous injection and tumor growth and cell apoptosis observed.Results Premature DC had a low expression of CD83 and CD86.In vivo,delayed growth of OVCAR3 xenografts was observed after immunotherapy with CTL induced by DC pulsed by CpG ODN and CA125.The inhibition rate of tumor was 50.71％ and it was better than CpG ODN-pulsed and CA125-pulsed groups (P ＜ 0.05).Cell apoptotic rate was (29.6 ± 3.0)％ in CpG ODN + CA125-pulsed group versus (21.8 ± 2.7)％ in CpG ODN-pulsed group.And both were more than those of unpulsed and CA125-pulsed groups (P ＜ 0.05).Conclusion CTL induced by DC sensitized by CpG ODN and CA125 can inhibit the growth of ovarian carcinoma xenografts and promote tumor cell apoptosis.