顺铂预处理化疗通过免疫调节增强CIK细胞对B16恶性黑色素瘤的抑制作用  

Cisplatin enhances the antitumor activity of cytokine-induced killer cells through modulation of immune cells

作　　者：陈景[1] 黄香[1] 宋海珠[1] 陈龙邦[1] 

机构地区：[1]南京大学医学院临床学院南京军区南京总医院肿瘤内科,南京210002

出　　处：《癌症进展》2011年第6期631-638,645,共9页Oncology Progress

基　　金：国家自然科学基金项目(No30872979);南京军区医学科研课题(09MA080)

摘　　要：目的观察顺铂(Cisplatin,DDP)预处理化疗联合CIK细胞对B16恶性黑色素瘤的抑制作用,探讨DDP预处理化疗增强细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK cells)抑瘤作用的潜在机制。方法建立C57BL/6小鼠B16黑色素瘤模型,测量肿瘤体积,绘制肿瘤生长曲线;免疫组化观察肿瘤组织调节性T细胞(regulatory T cells,Treg cells)的浸润;流式细胞术观察DDP预处理化疗对CIK归巢至肿瘤引流淋巴结(tumordraining lymph nodes,TDLN)、肿瘤组织的动态影响、树突状细胞(dendritic cells,DC)、髓系来源抑制细胞(mye-loid-derived suppressor cells,MDSC cells)的动态变化。结果 DDP预处理化疗联合CIK细胞显著抑制B16恶性黑色素瘤的生长(P<0.05);DDP预处理化疗减少肿瘤组织中Treg细胞的浸润;增强CIK细胞归巢至肿瘤引流淋巴结、肿瘤组织的能力;增加骨髓、外周血及脾脏组织中DC的比例(P<0.05);降低外周血、骨髓、脾脏组织及TDLN中MDSC的比例(P<0.05)。结论顺铂预处理化疗可通过免疫调节增强CIK细胞对B16恶性黑色素瘤的抑制。Objective To observe the tumor inhibition of DDP preconditioning combined with cytokine-induced killer cells（CIKs） in mice-bearing B16 melanoma model and to elucidate the underlying mechanisms DDP precondition for depressing tumor growth of CIKs.Methods Murine melanoma models were made and tumor size was measured as indicators of therapeutic response.The numbers of Treg infiltrating in tumor tissue were detected through immunohistochemical analysis.The percentages of dendritic cells（DC）,myeloid-derived suppressor cells（MDSC） and CIK cells in various tissues were analyzed through flow cytometry.Results The combination of DDP preconditioning chemotherapy and CIK cells significantly inhibited the growth of B16 melanoma（P0.05）.Pretreatment with DDP decreased the Treg in the local tumor tissues.DDP facilitated CIK cells homing to tumor tissues and TDLN.DDP up-regulated the percentages of DC in bone marrows,peripheral bloods and spleen tissues and diminish the levels of MDSC in bone marrows,peripheral bloods,spleen tissues TDLN.Conclusion DDP preconditioning chemotherapy can enhance the antitumor activity of CIK cell therapy in B16 melanoma model through modulation of endogenous and exogenous immune cells in various tissues.

关 键 词：预处理化疗 细胞因子诱导的杀伤细胞 调节性T细胞 树突状细胞 髓系来源抑制细胞 

分 类 号：R730.261[医药卫生—肿瘤] R730.53[医药卫生—临床医学]