肺癌TIL抗瘤活性、表型分析及临床应用的初步观察  

Clinical research on the antitumor activity and phenotype of tumor infiltrating lymphocytes for treatment of lung cancer

作　　者：张毅[1] 李世业[1] 赖百塘[2] 汪蕙[2] 湛秀萍[2] 刘桂枝[2] 王月[2] 

机构地区：[1]北京市结核病胸部肿瘤研究所医院胸外科,101149 [2]北京市结核病胸部肿瘤研究所医院细胞生物室,101149

出　　处：《中国肺癌杂志》2001年第5期336-339,共4页Chinese Journal of Lung Cancer

摘　　要：目的　从肺癌患者手术切除的肿瘤组织中分离出肿瘤浸润淋巴细胞 (TIL) ,经rIL 2体外激活培养 ,研究TIL对瘤细胞的杀伤活性及其表型变化 ,并对其回输后的毒副反应及患者免疫功能变化进行了观察。方法　从 5 1例肺癌患者手术切除的实体瘤中分离得到TIL ,并经 10 %人AB血清RPMI 16 40液培养。 12例在培养前、后应用 3H TdR释放实验测定TIL对自体瘤细胞和 80 1 D细胞的杀伤作用 ,13例用间接免疫荧光法测定了淋巴细胞表型CD3+ 、CD4+ 、CD8+ 比例的变化。 15例患者静脉输注了活化的自体TIL。结果　TIL在培养第 2 5天左右对自体瘤细胞和 80 1 D细胞的杀伤力比培养当天有显著性提高 ;淋巴细胞表型分析示CD3+ 、CD8+ 比例在培养过程中有明显提高 ,而CD4+ 比例和CD4+ /CD8+ 比值变化不大 ;自体回输的 15例患者一般状况好 ,无明显毒副反应 ,辅助检查无异常改变 ,免疫功能增强 ,复查血尿常规、生化、心肺功能等均无异常改变 ,远期疗效正在观察中。结论　大部分病例短期即可回输TIL ,且毒副反应小 ,因此肺癌TIIL过继免疫治疗是一种值得在临床进一步研究的免疫治疗方法。Objective To evaluate the feasibility and toxicity of the infusion of tumor infiltrating lymphocytes (TIL) with rIL 2 in patients with lung cancer. Methods TILs derived from tissue samples which obtained from the surgically removed tumors of 51 patients were cultivated in vitro. Fifteen patients were infused with 0.2×10 9 to 1.62×10 9 TIL cells intravenously at 2 8 weeks after operation and rIL 2 was inhaled into lung at dose of 3×10 5?U/day for 3 days. TIL cytolytic activities on day 0 and day 25th after incubation were assessed with 3H TdR release assay in vitro while the positive proportion of phenotypes of TIL were estimated with indirect immunofluorescence technique. Results The cytolytic activity of TIL against autologous tumor cell and 801 D cell line after incubation (50.35% and 42.81% respectively) was significantly higher than that before incubation (13.01% and 11.46% respectively) (P<0.05). There was no apparent difference of the cytolytic activity between autologous tumor cell group and 801 D cell line group. The percentage of CD 3 + and CD 8 + TILs after culture was significant higher than that before cultivation(P<0.05) and there was no change in the percentage of CD 4 + TILs and the ratio of CD 4 +/CD 8 +. Adverse effects were mild, only 3 of 15 patients had fever, headache, and nausea immediately after infusion of TIL and then recovered within several hours. Others had no any side effects. The immunity function of all patients was improved after infusion. Conclusion The result suggests that the infusion of expanded TILs in vitro, derived from surgical samples, is feasible and safe in patients with locally advanced lung cancer.

关 键 词：肺肿瘤 肿瘤浸润淋巴细胞 白细胞介素-2 过继免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]