目的：评价重组腺病毒载体编码基因修饰的自体树突状细胞（dendritic cell，DC）联合细胞因子诱导的杀伤（cytokine-induced killer，CIK）细胞（DC-CIK）治疗中晚期食道癌的临床疗效和安全性及其对食道癌患者外周血淋巴细胞亚群的影响。方法：采集2011年5月至2013年5月解放军第307医院收治的20例中晚期食道癌患者的PBMC，经实验室的体外培养诱导产生CIK细胞和DC，并将重组腺病毒载体编码的 survivin和muc-1 基因转染DC 。采集PBMC后第7、9、11、13天给患者皮下注射（3~10）×107个 DC（1 ml），第11、13天静脉回输(2~15)×109个CIK细胞（100 ml），每疗程间隔3个月，直至疾病进展，观察临床疗效和不良反应。分别于免疫治疗前1周和每疗程完成后的1个月取患者外周血，流式细胞术检测淋巴细胞亚群变化。结果：20例中晚期食道癌患者经DC-CIK治疗后，1例CR、6例PR、6例SD、7例PD；客观反应率为35%，疾病控制率为65%；经细胞免疫治疗后Th1\[（14.5±13.3）% vs （3.6±5.9）%， P <0.05\]、Th2\[（1.0±0.7）% vs （0.6±0.5）%， P <0.05\]细胞比例显著增加。治疗过程中20例患者均未出现发热和寒颤等相关不良反应。结论：DC-CIK细胞免疫治疗可改善中晚期食道癌患者的免疫抑制状态，提高患者的抗肿瘤免疫效应，无明显不良反应。

Objective: To evaluate the safety and clinical efficacy of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cells in the treatment of esophagus cancer and its effect on the lymphocyte subsets of peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were collected from 20 patients with stage Ⅱ-Ⅳ esophagus cancer who were admitted to the Academy of Military Medical Sciences-Affiliated Hospital in Beijing between May 2011 and May 2013. Non-adherent PBMCs were induced to develop into CIK cells by IFN-γ, IL-2 500 U/ml and Anti-CD3 and adherent PBMCs were induced to develop into DCs by TNF-α, followed by transfection with surviving and muc-1 . On days 7, 9, 11, and 13, respectively, after PBMCs collection, DCs (3-10)×107 in 1 ml PBS) were given subcutaneously and days 11 and 13 CIK cells (2-15)×109 in 100 ml PBS. This treatment regimen was repeated at an interval of 3 months until substantial remission was achieved. Clinical outcomes and adverse effects were recorded during the treatment period. One week before treatment and one month after each treatment cycle, peripheral blood was collected and lymphocyte subsets were analyzed by flow cytometry. Results: Complete remission occurred in one case and partial remission in 6 cases while the disease remained at a stable state in 6 cases and at a progressive state in 7 cases after treatment. The overall response rate was 35% and the disease control rate was 65%. Treatment with CIKs and DCs significantly increased the percentage of both Th1 (\[14.5±13.3\]% vs \[3.6±5.9\]% and Th2 (\[1.0±0.7\]% vs \[0.6±0.5\]% as compared with the vehicle control ( P <0.05). No evident adverse events were observed. Conclusion: Infusion of DCs and CIK cells may improve the immunosuppression status and enhance the anti-tumor immunity in patients with stage Ⅱ-Ⅳ esophagus cancer, thereby having potential clinical implications.

国家科技重大专项“十二五”计划基金资助项目（No.2009zx09503）