肿瘤浸润性淋巴细胞在白细胞介素-2、-4协同下局部过继免疫治疗膀胱癌的实验研究

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。

Effects of local immunotherapy against bladder carcinoma by tumor-infiltrating lymphocytes combined with interleukin (IL)-2 and/or IL-4

Objective To investigate the effects of local immunotherapy against bladder carcinoma and the regulation for systemic antitumor immune response by tumor-infiltrating lymphocytes (TIL) combined with interleukin (IL)-2 and/or IL-4.Methods Tumour model was developed in BTT739 mice.Suspensions of TIL were prepared from T739 murine bladder carcinoma.Direct intratumoural injection of TIL combined with IL-2 and/or IL-4 against murine bladder transitional cell carcinoma were carried out according to orthogonal design experimental method.Tumor volume was measured regularly.The NK cell activity and T-lymphocytes stimulation index were investigated by MTT colorimetric assay.Murine ultrastructures were observed in each group after immunotherapy.Results Two-week immunotherapy correlated to TIL reduced tumor volume and augmented splenic NK cell activity and T-lymphocytes proliferation to varying degrees as compared with control group (P<0.05).TIL/IL-2 therapy could significantly inhibit the growth of tumor and the synergic antitumor effects were observed one week after immunotherapy (P<0.05).Furthermore,the NK cell activity and T-lymphocytes stimulation index were markedly increased (P<0.05).TIL/IL-2/IL/4 therapy also showed strong antitumor action,but not statistically significantly different from that in TIL/IL-2 group (P>0.05).Ultrastructural observation showed obvious disruption of cancer cells resulted from TIL.Conclusion Local immunotherapy using TIL in combination with different cytokines especially IL-2 can produce more significant anti-bladder carcinoma effects and enhance systemic antitumor immune responses.