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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 the biological 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, nature and site of the tumor. TIL derived from connective tissue and stroma was predominantly CD3 + CD4 +, mainly CD3 + CD8 + around tumor and small vessel, IL2 The concentration of TIL immunological properties have a great impact. After being amplified by rIL 2, the ability of TIL to produce various cytokines, such as IL 2, TNF α, IFN γ, and the activity of killing tumor cells are obviously increased. Additional anti-CD3 mAb or PHA (appropriate concentration), TIL cytokine expression can be further enhanced. TIL combined with phosphoramidite or IL 2 in patients with advanced ovarian cancer can significantly improve the phenotype of peripheral blood cells in patients with a certain effect. Conclusion: After TIL is amplified by rIL 2 in vitro, its immunological activity is obviously 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.