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目的 研究卵巢癌浸润淋巴细胞(TIL) 在体外扩增后免疫学特性,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CD+3 、CD+4 为主,肿瘤组织和小血管周围以CD+3 、CD+8 为主,体外IL2 的浓度对TIL的免疫学特性有很大的影响。经rIL2 扩增后,TIL分泌产生IL2、TNFα、IFNγ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联合环磷酰胺或IL2 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rIL2 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一种有效治疗手段
Objective To investigate the immunological characteristics of infiltrating lymphocytes (TIL) in vitro and to evaluate the potential of TIL in the treatment of advanced ovarian cancer. Methods The cell phenotype of TIL was analyzed by flow cytometry. The ability of TIL to secrete cytokines and the activity of killing tumor cells were studied by molecular biology and immunological methods. Results TIL cell phenotype may be related to the type of tumor, the nature of the tumor and the site of the tumor. TIL derived from connective tissue and stroma was predominantly CD + 3 and CD + 4. CD + 3 and CD + 8 were mainly located around the tumor and small vessels. IL- 2 concentration on the immunological characteristics of TIL have a great impact. After the expansion of rIL 2, TIL secretion produce IL 2, TNF @, IFN γ and other cytokines and cytotoxic activity were significantly increased. Additional anti-CD3 mAb or PHA (appropriate concentration), TIL cytokine expression can be further enhanced. TIL combined with cyclophosphamide or IL 2 treatment of advanced ovarian cancer patients, can significantly improve the phenotype of patients with peripheral blood cells, with a certain effect. Conclusion TIL in vitro by rIL 2 amplification, immunological activity was significantly improved. The regression of tumor cells in vivo may not mainly directly kill the tumor cells through the input TIL, but rather enhances the cellular immune activity and immunomodulatory capacity largely depending on their secretion of various cytokines. TIL-assisted other therapies can be an effective treatment for patients with advanced ovarian cancer