自体树突细胞联合细胞因子诱导的杀伤细胞治疗转移性肾癌的疗效分析及随访观察

Autologous dendritic cells combined with cytokine-induced killer cells in the treatment of metastatic renal cell carcinoma

目的评价自体树突细胞(DC)联合细胞因子诱导的杀伤细胞(CIK)治疗转移性肾癌的临床疗效、免疫功能变化及随访结果。方法采集27例转移性肾癌患者的外周血单个核细胞(PBMC),经实验室体外培养诱导产生DC和CIK细胞,经无菌检测、流式细胞术表型鉴定及细胞计数后回输给患者。于第7、9、11、13天皮下注射DC,第11、13天静脉回输CIK,每疗程间隔3个月,直至疾病进展,观察临床疗效及免疫功能的变化。结果 27例转移性肾癌患者经DC-CIK治疗后的客观反应率为37%,疾病控制率为85%,2年总生存率为81.5%。与治疗前比较,治疗后患者外周血CD3^+CD4^+CD8–、CD3^+CD4–CD8^+、CD3^+CD19–、CD3–CD19^+、CD3–CD16^+CD56^+、CD3^+CD16^+CD56^+、CD3^+HLA-DR–、CD3^+HLA-DR^+、CD3^+CD28^+CD8^+细胞亚群及Th2细胞无显著变化(P>0.05),Th1细胞有升高趋势(P<0.05),多次治疗后CD3^+CD4^+CD25^+T细胞(即调节性T细胞,Treg细胞)有降低的趋势(P<0.05)。治疗过程中27例患者均未出现明显不良反应。结论 DC-CIK细胞免疫治疗为转移性肾癌患者提供了一种新的安全有效的治疗方法,可改善转移性肾癌患者的免疫抑制状态,提高患者的抗肿瘤免疫反应,无明显不良反应。

Objective To evaluate the clinical efficacy, the immune function and follow-up obser vation of autologous dendritic cells（DCs） combined with cytokine-induced killer（CIK） cells in the treatment of metastatic renal cell carcinoma. Methods Peripheral blood mononuclear cells（PBMCs） were collected from 27 patients with metastatic renal cell carcinoma, and cultured in vitro to produce DCs and CIK cells. After sterility test, phenotypic characterization by flow cytometry and cell count, the produced DCs and CIK cells were then returned to the patient. DCs were given subcutaneously on day 7, 9, 11 and 13 respectively, after PBMCs collection, and CIK cells were given intravenously on day 11 and 13 respectively. This treatment regimen was repeated at a 3 months interval until the disease progresses. Clinical outcomes and immune function were recorded during the treatment period. Results After DCs-CIK cells treatment, clinical efficacy showed an objective response rate（ORR） of 37%, a disease control rate（DCR） of 85% and 2 years overall survival rate of 81.5%. There were no significant changes of T cell subsets including CD3^＋CD4^＋CD8^-, CD3^＋CD4–CD8^＋, CD3^＋CD19^-, CD3^-CD19^＋, CD3^-CD16^＋CD56^＋, CD3^＋CD16^＋CD56^＋, CD3^＋HLA-DR^-, CD3^＋HLA-DR^＋, CD3^＋CD28^＋CD8^＋ and Th2 cells except CD3^＋CD4^＋CD25~＋ T cells（Treg cells） and Th1 in peripheral blood between pre- and post-treatment. No serious adverse events were observed. Conclusion DCs-CIK cells immunotherapy provides a safe and effective treatment approach for patients with metastatic renal cell carcinoma, and may improve the immunosuppression status and enhance the anti-tumor immunity without obvious adverse reaction.