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目的 观察膀胱癌肿瘤浸润性淋巴细胞 (TIL)联合不同细胞因子瘤灶内过继免疫抗癌的效应及对机体全身抗肿瘤免疫机制的影响。方法 建立BTT73 9动物模型 ,分离、培养TIL。采用正交设计实验方法 ,将TIL、白细胞介素 (IL) 2、 4及三因素交互组合悬液分别直接注射至瘤体内 ,定期测量肿瘤体积 ,免疫治疗 2周后检测NK细胞活性、T淋巴细胞转刺激指数 ,观察组织学及超微结构变化。结果 比较对照组 ,治疗 2周时各TIL相关组均不同程度抑制了膀胱肿瘤体积的增长 ,且NK细胞活性及T淋巴细胞转化增殖能力得以提高 (P <0 .0 5 )。TIL/IL 2疗法明显抑制了瘤体的增长 ,免疫治疗 1周后即表现出协同增强效应 (P <0 .0 5 ) ,而NK细胞活性及T淋巴细胞转刺激指数也显著提高 (P <0 .0 5 )。TIL/IL 2 /IL 4组获得了较强的抗癌功效 ,但与TIL/IL 2组差异无显著性 (P >0 .0 5 )。超微结构变化显示出TIL强烈的溶癌现象。结论 TIL在细胞因子特别是IL 2协同下瘤灶内注射的局部免疫疗法 ,具有较强的抗膀胱癌效应 ,并显著提高了机体全身抗瘤免疫功能。
Objective To observe the effect of adoptive immunity anticancer in bladder cancer tumor infiltrating lymphocytes (TIL) combined with different cytokines and its effect on systemic anti-tumor immunity. Methods BTT73 9 animal model was established, TIL was isolated and cultured. The orthogonal experimental design was used to directly inoculate TIL, interleukin (IL) 2, 4 and three-factor interactive combination into the tumor respectively. The volume of the tumor was measured regularly. The NK cell activity, Stimulation index of cells, histological and ultrastructural changes were observed. Results Compared with the control group, the TIL-related groups all inhibited the growth of bladder tumor to varying degrees at 2 weeks of treatment, and the activity of NK cells and the ability of T lymphocyte transformation and proliferation to increase (P <0.05). TIL / IL 2 treatment significantly inhibited the growth of the tumor, and showed synergistic enhancement after 1 week of immunotherapy (P <0.05), while NK cell activity and T lymphocyte stimulating index were also significantly increased (P < 0 .0 5). TIL / IL 2 / IL 4 group had a stronger anti-cancer effect, but no significant difference with TIL / IL 2 group (P> 0.05). Ultrastructural changes show a strong TIL cancer phenomenon. CONCLUSION: Local immunotherapy of TIL with intra-tumor injection of cytokines, especially IL-2, has strong anti-bladder cancer effect and significantly enhances systemic anti-tumor immune function.