卵巢癌浸润淋巴细胞的生物学特性研究  

Study on biological character of tumor-infiltrating lymphocytes in ovarian carcinoma

作　　者：童善庆[1] 王建华[2] 李彪如[1] 丁健青[1] 胡宝瑜[1] 朱佑明[1] 陆德源[1] 华祖德[3] 陆静[3] 

机构地区：[1]上海第二医科大学微生物学教研室,上海200025 [2]上海第二医科大学分子生物实验室,99级博士生上海200025 [3]上海第二医科大学附属瑞金医院妇产科,上海200025

出　　处：《中国免疫学杂志》2000年第3期131-134,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金!( 3 93 70 70 6)资助

摘　　要：目的 :研究卵巢癌浸润淋巴细胞 (TIL)在体外扩增后生物学特性 ,评估TIL用于晚期卵巢癌治疗的前景。方法 :利用流式细胞仪分析TIL的细胞表型 ,使用分子生物学和免疫学方法研究TIL分泌细胞因子的能力和杀伤肿瘤细胞的活性。结果 :TIL细胞表型的差异可能与肿瘤的种类、性质、取材部位有关 ,结缔组织、基质中来源的TIL以CD3+ CD4+ 为主 ,肿瘤组织和小血管周围以CD3+ CD8+ 为主 ,体外IL 2的浓度对TIL的免疫学特性有很大的影响。经rIL 2扩增后 ,TIL分泌产生IL 2、TNF α、IFN γ等多种细胞因子能力及杀伤肿瘤细胞的活性均有明显提高。再加入抗CD3单抗或PHA(合适浓度 ) ,TIL细胞因子表达可进一步增强。TIL联合磷酰胺或IL 2治疗晚期卵巢癌患者 ,可显著改善患者外周血细胞表型 ,具有一定的疗效。结论 :TIL在体外经rIL 2扩增后 ,免疫活性有明显提高。体内肿瘤细胞的消退可能主要并不是通过输入的TIL直接杀伤肿瘤细胞 ,而是在很大程度上依靠其分泌多种细胞因子增强了机体细胞免疫活性和免疫调节能力。TIL辅助其它疗法可成为晚期卵巢癌患者的一种有效治疗手段。Objective:To study biological character of tumor infiltrating lymphocytes on post in vitro expansion in ovarian carcinoma , and evaluate prospects of using TIL treatment of advanced stage of ovarian carcinoma .Methods:Cellular phenotype changes in TIL were analyzed by flow cytometry . By means of molecular biology and immunologic methods, ability of secrete cytokines and activities of anti tumor in TIL were studied.Results:Difference of cellular phenotype in TIL is probably related to type,feature,and resource of tumor. CD3 +CD4 + is dominant in TIL from connective tissue and parenchyma.CD3 +CD8 + is dominant in TIL from tumor tissue and around microvessels . Concentration of rIL 2 in vitro plays a significant role in immunologic character of TIL. By means of rIL 2 expansion in vitro ,TIL has apparently been improved in competence of secreting some cytokines ,such as IL 2、TNF α、IFN γ,and anti tumor activities.TIL was more stimulated by adding anti CD3 or PHA (suitable concentration), which significantly increased its ability to secreting cytokines. Treatment with TIL+CTX or TIL+ rIL 2, could apparently improve phenotype in peripheral blood cell patients , with somewhat effects.Conclusion:Immunologic activity of TIL in vitro are apparently improved by rIL 2 expansion. Tumor regression , by means of infusion TIL, is not largely attributed to direct cytotoxicity to tumor cell , but indirectly and partly augmenting cellular activities and abilities of immunomodulation in patients with ovarian carcinoma ,through secreting multiply cytokines.

关 键 词：卵巢肿瘤 淋巴细胞 肿瘤浸润 TIL 

分 类 号：R737.31[医药卫生—肿瘤]