DC-CIK细胞辅助治疗黑色素瘤的临床疗效及预后分析

Clinical efficacy and prognostic analysis of DC-CIK cytotherapy in the adjuvant treatment of melanoma

目的回顾性分析树突状细胞(dendritic cell,DC)联合细胞因子诱导的杀伤(cytokine-induced killer,CIK)细胞治疗50例黑色素瘤患者的临床疗效和安全性,并对影响DC-CIK治疗黑色素瘤患者预后的危险因素进行分析,为临床研究提供依据。方法采集2011年10月至2017年10月解放军第81医院肿瘤生物治疗中心收治的50例黑色素瘤患者的外周血单个核细胞(peripheral blood mononuclear cell,PBMC),经实验室体外诱导培养DC和CIK细胞,DC通过多肽组合致敏后与CIK细胞回输给患者,观察DC-CIK细胞治疗黑色素瘤患者的临床疗效和安全性。结果 50例黑色素瘤患者经DC-CIK细胞免疫治疗后,1年生存率为67%,2年生存率为58%,3年生存率为52%,5年生存率为41%,中位总生存期(overall survival,OS)为28个月,中位无进展生存期(progress free survival,PFS)为23个月。细胞治疗后患者外周血CD4^+CD25+Treg细胞比例显著下降(P=0.026 3),CD3+细胞比例明显上升(P=0.012 3),CD3+CD4^+、CD3+CD8+细胞比例及CD4^+/CD8+比值无显著变化(P>0.05)。单因素分析显示KPS评分、细胞治疗疗程、TNM分期、是否发生远处转移、是否发生淋巴结转移以及血清LDH水平为DC-CIK辅助治疗黑色素瘤预后的影响因素(P<0.05);多因素分析显示年龄、血清LDH水平与DC-CIK辅助治疗黑色素瘤患者的预后相关(P<0.05)。结论DC-CIK细胞治疗可以延长黑色素瘤术后患者的生存期,改善生活质量,是一种有效的辅助治疗方式,无严重不良反应,安全可行。

This study was designed to retrospectively analyze the efficacy and safety of the cytotherapy of dendritic cells（DCs） combining with cytokine-induced killer（CIK） in the treatment of melanoma. Firstly, we collected the peripheral blood mononuclear cells（PBMCs） of 50 patients with melanoma from the Tumor Biotherapy Center of the 81 stHospital of PLA to culture the DC and CIK cells in vitro. Then the DCs were sensitized with polypeptide complexes and transfused with CIK together to patients. At last, we observed the survival condition and the immune status of these patients. Data showed that after the DC-CIK immunotherapy, patients＇ 1-year overall survival rate was 67%, 2-year survival rate was 58%, 3-year survival rate was 52%, 5-year survival rate was 41%.The median survival time was 28 months while the median progression-free survival was 23 months. The proportion of CD4~＋CD25＋cells in peripheral blood of melanoma patients with cell therapy markedly decreased（P=0.026 3）, the proportion of CD3＋cells significantly increased（P=0.012 3）, and no significant alterations were found inthe proportion of CD3＋CD4~＋, CD3＋CD8＋cells and CD4~＋/CD8＋ratio（P0.05）. Single factor analysis showed thatKarnofsky score, treatment cycle, TNM staging,metastasis, lymph node metastasis, and the LDH level in serum were all influence factors for the prognosis of melanoma patients with DC-CIK cytotherapy（P0.05）. Multivariate analysis with Cox model indicated age and the LDH level in serum were correlated with the survival time of these patients（P0.05）. The results demonstrated that DC-CIK cytotherapy can prolong the survival time and improve the quality of life in melanoma patients, which is a effective and feasible adjuvant therapy without serious adverse reaction.