树突状细胞激活的肿瘤浸润淋巴细胞抗小鼠乳腺癌研究  

Effects of tumor infiltrating lymphocytes stimulated by dendritic cells on breast cancer in mice

作　　者：刘剑勇[1] 张志明[1] 赵荫农[1] 吕丽琼[1] 张春燕[1] 唐凯[1] 张力图[1] 吴飞翔[1] 黄山[1] 

机构地区：[1]广西医科大学附属肿瘤医院肝胆乳腺外科,南宁530021

出　　处：《免疫学杂志》2007年第4期390-394,398,共6页Immunological Journal

基　　金：广西科学基金项目资助(桂科青0339033)

摘　　要：目的探讨C127细胞全细胞性抗原致敏的DC激活的TIL体外抗小鼠乳腺癌活性,并将C127细胞全细胞性抗原致敏的DC激活的TIL(C127-DC-TIL)过继免疫荷瘤小鼠,研究其对C127荷瘤小鼠免疫功能的影响及抑瘤作用。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C127细胞、MA782细胞和B16细胞的杀伤活性;检测应用C127-DC-TIL后荷瘤小鼠的脾淋巴细胞的NK、LAK、CTL活性、血清TNF活性、抑瘤作用以及瘤体病理改变,并与对照组相比较。结果①C127-DC-TIL具有很强的对C127细胞杀伤活性[杀伤率为(70.21±2.86)%],明显高于其对MA782和B16细胞的杀伤活性[杀伤率分别为(51.31±3.25)%,(31.41±2.65)%],也明显高于未经DC激活的TIL、C127-DC-脾淋巴细胞和未经DC激活的脾淋巴细胞对C127细胞杀伤活性[杀伤率分别为(48.30±2.97)%,(47.76±3.43)%和(17.23±2.56)%]和对MA782细胞杀伤活性[杀伤率分别为(38.52±2.87)%,(36.62±2.75)%和(18.07±2.40)%]以及对B16细胞杀伤活性[杀伤率分别为(25.38±2.63)%,(24.82±2.81)%和(17.34±2.81)%],同时B16细胞全细胞性抗原致敏的DC激活的TIL(B16-DC-TIL,TIL来源于C127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。②C127-DC-TIL可明显诱导提高荷瘤小鼠脾淋巴细胞NK、LAK和CTL活性[活性分别为(32.21±1.24)%(、30.35±1.72)%和(37.43±1.54)%],并可检测到血清TNF水平明显上升[血清TNF水平为(38.41±1.77)U/ml],它们均达正常对照组水平,与未经DC激活的TIL组、C127-DC-脾淋巴细胞组、未经DC激活的脾淋巴细胞组、生理盐水组分别对应比较,差异均有显著性(P<0.01)。该组瘤体内淋巴细胞浸润程度也高于对照组,其瘤体生长明显受到抑制。结论①C127-DC-TIL可产生很强的体外针对C127细胞的特异性杀伤活性。②C127-DC-TIL具有很强的特异性抗小鼠�Objective To investigate the effects of C127-DC-TIL [tumor infdtrating lymphocytes （TILs） stimulated by dendritic cells （DCs） that were sensitized by C127 cell antigen] on carcinoma cells in vitro and to explore its influence on immune and tumor progression in mice.Methods DCs isolated from mouse bone marrow were sensitized by granulocyte/macmphage colony stimulating factor （GM-CSF）, interleukin-4 （IL-4）, and tumor antigen. Then the TILs were stimulated by the DCs, and the effects of the TILs on C127, MA782, and B16 cells were observed in vitro. The activities of splenocyte NK, LAK, CTL, serum TNF, inhibition of the tumor progression and tumor pathologic change of tumor-bearing mice were assayed respectively after treatment with C127-DC-TIL, and comnared with control groups. Results C127- DC-TIL had very high killing effects on C127 cells [killing rate： （71.31 ± 3.11） % ], which were significantly higher than those on MA782 and B16 cells. Meanwhile, the killing rates of C127, MA782, and B16 cells by DCs-stimulated TILs were significantly higher than those by the TILs unstimulated by DCs and the splenocytes stimulated or unstimulated by DCs （P 〈 0.01 ）. TILs from C127 rumor stimulated by B16 rumor antigen-activated DCs had relative low killing effects on B16 cells. The activities of splenocyte NK, LAK, CrL, and serum TNF of tumor-bearing mice could be enhanced obviously by C127-DC-TIL, even reached the level of normal group, which had significant difference comparing with TILs unstimulated by DCs group, splenocytes stimulated or unstimulated by DCs groups, as well as normal saline group （ P 〈 0.01 ）. The level of lymphocytes infdtrating in tumor of the group was higher than those of the control groups, and tumor progression in tumor-bearing mice also was significantly inhibited （ P 〈 0.01 ）. Conclusion C127-DC-TIL has very high specific killing effects on C127 cells; C127-DC-TIL has very strong specific anti-mouse breast cancer effects.

关 键 词：树突状细胞 肿瘤浸润淋巴细胞 C127细胞 杀伤活性 小鼠乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]