CAJ | 학술논문

目的通过抑制荷瘤小鼠体内调节性T细胞(TregFoxp3+),探讨其增强DC/HCC融合细胞疫苗诱导抗肝癌免疫作用的相关机制.方法皮下建立小鼠肝癌模型,24只小鼠随机分为4组:(1)环磷酰胺联合疫苗组[环磷酰胺(CTX)+ VAC]；(2)疫苗组(VAC)；(3)单纯环磷酰胺组(CTX)；(4)对照组.各组治疗后,取外周血测定CD8+及CD4+淋巴细胞比例,同时取肿瘤组织及脾脏组织分别行苏木素-伊红(HE)染色和免疫组织化学观察肿瘤坏死和CD8+细胞及Treg+细胞的浸润,并用细胞计数试剂盒(CCK-8)检测脾脏淋巴细胞特异性细胞毒T淋巴细胞(CTL)活性.结果与其他各组比较,CTX+ VAC组外周血CD4+及CD8+细胞比例增高[ CTX+ VAC:17.50％、14.69％；VAC:16.17％、13.07％；CTX:12.17％、11.59％；对照组:12.24％、11.16％]；肿瘤组织可见大量肿瘤细胞坏死,脾脏组织中Foxp3+细胞浸润减少,CD8+细胞浸润增高,CTL对肿瘤细胞杀伤作用明显增强(P＜0.05).结论通过CTX抑制荷瘤小鼠微环境及外周血中的Treg细胞,可以明显增强DC/HCC融合疫苗对肿瘤的杀伤作用.
목적 통과억제하류소서체내조절성T세포(TregFoxp3+),탐토기증강DC/HCC융합세포역묘유도항간암면역작용적상관궤제.방법 피하건립소서간암모형,24지소서수궤분위4조:(1)배린선알연합역묘조[배린선알(CTX)+ VAC]；(2)역묘조(VAC)；(3)단순배린선알조(CTX)；(4)대조조.각조치료후,취외주혈측정CD8+급CD4+림파세포비례,동시취종류조직급비장조직분별행소목소-이홍(HE)염색화면역조직화학관찰종류배사화CD8+세포급Treg+세포적침윤,병용세포계수시제합(CCK-8)검측비장림파세포특이성세포독T림파세포(CTL)활성.결과 여기타각조비교,CTX+ VAC조외주혈CD4+급CD8+세포비례증고[ CTX+ VAC:17.50％、14.69％；VAC:16.17％、13.07％；CTX:12.17％、11.59％；대조조:12.24％、11.16％]；종류조직가견대량종류세포배사,비장조직중Foxp3+세포침윤감소,CD8+세포침윤증고,CTL대종류세포살상작용명현증강(P＜0.05).결론 통과CTX억제하류소서미배경급외주혈중적Treg세포,가이명현증강DC/HCC융합역묘대종류적살상작용.
Objective To explore whether the regulatory T cells (Treg) depletion can significantly enhance the DC/HCC fusion vaccine (VAC) to induce the antitumor immune responses against hepatocellular carcinoma (HCC).Methods Tumor bearing mice model was established subcutaneously.Then the mice were randomly divided into4 groups:(1) CTX +VAC group; (2) VAC group; (3) CTX group;(4) control group.All the mice in each group were sacrificed,and peripheral blood and spleen tissue were collected for detection of the percentage of CD8 + and CD4 + cells,spleen cytotoxic T-cell (CTL) activity assay and immune histological examnation.Results The percentage of CD4+ and CD8 + cells in the blood was significantly higher in VAC + CTX group than in other groups ( CTX + VAC:17.50％,14.69％ ;VAC:16.17％,13.07％; CTX:12.17％,11.59％; Control:12.24％,11.16％,P＜0.05).Tumor nercrosis and infiltration of CD8 + T cells were increased,and infiltration of Foxp3 + cells in the spleen tissue was reduced in CTX + VAC group as compared with other groups.And the spleen CTL activity was also significantly enhanced in CTX + VAC group (P ＜ 0.05 ).Conclusion Low dose CTX can significantly decrease the number of Treg in the tumor microenviroment and peripheral blood,which can obviously enhance the DC/HCC fusion cell vaccine to induce anti-tumor cytotoxic reaction.