卵巢癌浸润淋巴细胞的免疫学特性研究

STUDY ON IMMUNOLOGIC CHARACTERS OF TUMOR INFILTRATING LYMPHOCYTES IN OVARIAN CARCINOMA

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联合环磷酰胺或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。

PURPOSE To study immunologic characters 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 are analyzed by flow cytometry.By means of molecular biology and immunologic methods,ability of secreting cytokines and activities of anti tumor in TIL are studied.RESULTS Difference of cellular phenotype in TIL is probably related to type,feature,and source of tumor.CD + 3,CD + 4 is dominant in TIL from phoroplast and parenchyma.CD + 3,CD + 8 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 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 is more stimulated by adding anti CD 3 or PHA(suitable concentration),which makes its ability of secreting cytokines to be apparently increased.Treatment with TIL+CTX or TIL+rIL 2,can apparently improve phenotype in peripheral blood of patients,with some effect.CONCLUSIONS Immunologic activity of TIL in vitro are apparently improved by rIL 2 expansion.Tumor regression,by 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 multiple cytokines.