树突状细胞激活的肿瘤浸润性淋巴细胞体外特异性抗小鼠肝癌研究  

In vitro effects of tumor infiltrating lymphocytes stimulated by dendritic cells on hepatocellular carcinoma in mice

作　　者：张志明[1] 刘剑勇[1] 赵荫农[1] 袁卫平[1] 张力图[2] 张春燕[2] 李挺[1] 

机构地区：[1]广西医科大学附属肿瘤医院肝胆外科,南宁市530021 [2]广西医科大学附属肿瘤医院细胞与分子生物研究室

出　　处：《中华肝胆外科杂志》2005年第8期547-550,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：广西科学研究与技术开发计划攻关项目(桂科攻0143052)

摘　　要：目的树突状细胞(DC)是目前已知的功能最强的抗原提呈细胞(APC),可以向包括肿瘤浸润性淋巴细胞(TIL)在内的T淋巴细胞提呈抗原,并诱发细胞毒T淋巴细胞(CTL)反应。本文旨在探讨H22细胞和B16细胞全细胞性抗原致敏的树突状细胞激活的肿瘤浸润性淋巴细胞体外抗小鼠肝癌活性。方法从小鼠四肢长骨骨髓中获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白介素-4(IL-4)和肿瘤全细胞性抗原致敏DC,然后用DC激活TIL,观察TIL在体外对H22细胞、Hepal-6细胞和B16细胞的杀伤活性。结果经H22细胞全细胞性抗原致敏的DC激活的TIL具有很高的对H22细胞杀伤活性,杀伤率为(71·31±3·11)%,明显高于其对Hepal-6和B16细胞的杀伤活性[杀伤率分别为(50·11±3·03)%,(30·31±2·89)%];也明显高于未经H22细胞全细胞性抗原致敏的DC激活的TIL、DC激活的脾淋巴细胞和未经DC激活的脾淋巴细胞对H22细胞杀伤活性[杀伤率分别为(49·80±3·21)%,(48·76±3·60)%和(19·23±2·71)%]和对Hepal-6细胞杀伤活性[杀伤率分别为(39·4±3·21)%,(38·62±2·87)%和(18·73±2·40)%]以及对B16细胞杀伤活性[杀伤率分别为(26·38±2·51)%,(25·82±2·70)%和(18·34±3·01)%],同时经B16细胞全细胞性抗原致敏的DC激活的TIL(来源于H22瘤体)也可诱导相对较低的对B16细胞的特异性细胞杀伤活性。结论来源于H22瘤体的TIL经H22细胞全细胞性抗原致敏的DC激活后可产生很强的针对H22细胞的特异性杀伤活性,明显高于其他各组,说明DC能诱导TIL产生高效而特异的体外抗小鼠肝癌免疫。Objective To investigate the effects of tumor infiltrating lymphocytes （TILs） stimulated by dendritic cells （DCs） on hepatocellular carcinoma （HCC） in vitro. Methods DCs were isolated from mouse bone marrow and stimulated by granulocyte/macrophage colony stimulating factor （GM-CSF）, interleukin-4 （IL-4） and tumor antigen. Then the TILs were stimulated by the DCs. Finally, the effects of the TILs on H22, Hepal-6 and B16 cells in vitro were observed. Results The TILs stimulated by DCs had very high killing effects on H22 cells and the killing rate was （71.31 ± 3.11）%, which were significantly higher than those on Hepal-6 and B16 cells. Meanwhile, the killing rates of H22, Hepal-6 and B16 cells by TILs stimulated by DCs was significantly higher than those by TILs not stimulated by DCs, splenocytes stimulated by DCs and splenocytes not stimulated by DCs （P 〈0. 01）. TILs frm H22 tumor stimulated by DCs which activated B16 tumor antigen before had rela- tively low killing effects on B16 cells. Conclusions TILs stimulated by DCs can exert significant killing effects on H22 cells, which indicates that DCs can induce TILs to produce efficient and specific anti-tumor immunity for HCC in mice in vitro.

关 键 词：癌 肝细胞 树突状细胞 肿瘤浸润性淋巴细胞 H22细胞 B16细胞 杀伤 活性 免疫 树突状细胞激活 小鼠肝癌 

分 类 号：R735.7[医药卫生—肿瘤] R735.2[医药卫生—临床医学]