自体不成熟树突状细胞胸腔内注射治疗化疗耐药的肿瘤患者恶性胸腔积液

Treatment of chemotherapy resistant malignant pleural effusion with injection of autologous immature dendritic cells

目的:观察体外扩增的不成熟树突状细胞(dendritic cells,DC)胸腔内注射对恶性胸腔积液的疗效和安全性。方法:从6例对化疗耐药的恶性胸腔积液患者采集外周血单个核细胞,体外细胞因子诱导培养获得不成熟DC,每4周患者胸腔内注射DC(5~10)×107个,连续3次为一疗程,观察治疗后患者胸腔积液的变化及治疗的不良反应,流式细胞仪检测胸水中T细胞、NK细胞亚群。结果:总体疗效为:CR 2例,PR 1例,SD 1例,PD 2例,有效率为50%(3/6),获益率(CR+PR+SD)为66.7%。2例CR均为肾癌患者,缓解时间达26周和147周;3例肺癌患者中1例PR、1例SD及1例PD;1例恶性胸膜间皮瘤PD;治疗中无严重不良反应发生。DC治疗后6例患者胸水中的T细胞百分率均较治疗前上升,但差异无统计学意义;NK细胞百分率较治疗前明显上升(P<0.05)。结论:采用无抗原加载的自体不成熟DC胸腔内注射治疗恶性胸腔积液的疗效肯定,可能主要是通过NK细胞介导,是一种安全、有效的治疗方法。

Objective: To evaluate the effect and safety of intrapleural injection of in vitro expanded immature dendritic cells( DC) for the treatment of malignant pleural effusion. Methods: Peripheral blood mononuclear cells were collected from 6 patients with chemo-resistant malignant pleural effusion and cultured with cytokines to expand immature DC in vitro. The cells were then intrapleurally injected into the patients( 5 ~ 10) × 107 every 4 weeks for 3 times as a course of treatment. The changes of pleural effusion and side effects in each patient were examined. T cell and NK cell subsets in the pleural effusion were analyzed by flow cytometry. Results: Overall,2 renal cell carcinoma patients had complete responses,1 lung cancer patients had partial response,1 lung cancer patients had SD,and 2 other patients had PD.Therefore,the response rate was 50%( 3 /6) and the benefit rate was 66. 7%. Duration of the response of the 2 renal cell carcinoma patients was 26 weeks and 147 weeks respectively. After DC treatment,the percentages of T and NK cells increased in the pleural effusion,but only the increase of NK cells is statistically significant. Conclusion: This pilot study indicated that intrapleural injection of none-antigen loaded immature DCs is well-tolerated,has positive effect on the management of malignant pleural effusions,which is likely mediated by NK cells. These results suggest that DC immunotherapy is a promising method to treat malignant pleural effusions in the future.