目的： 探讨树突状细胞（dendritic cell，DC）联合细胞因子诱导的杀伤（cytokine-induced killer，CIK）细胞治疗局部晚期和晚期胰腺癌的安全性和有效性。 方法： 采集2011年7月至2012年5月在解放军第81医院生物治疗科治疗的24例Ⅲ～Ⅳ期胰腺癌患者外周血单个核细胞（peripheral blood mononuclear cell，PBMC），体外诱导培养DC和CIK细胞。DC经胰腺癌细胞株（PANC-1）裂解物致敏后与CIK细胞回输至胰腺癌患者，观察DC-CIK细胞治疗前后患者外周血淋巴细胞亚群、血清肿瘤标志物的改变以及临床疗效。 结果： DC-CIK细胞治疗3个月后，胰腺癌患者外周血CD3+T细胞、CD8+T细胞和CD4+CD25+Treg细胞比例均显著下降（均P<0.05），CD4+/CD8+比值升高\[（1.1±0.7) vs (1.5±0.9)，P<0.05\]。血清肿瘤标志物CA19-9在治疗后1个月\[（382.8±277.7) vs (213.8±214.6)，P<0.05\]和治疗后3个月\[（213.8±214.6) vs (1540±118.2)，P<001）持续下降。24例患者无1例完全缓解，其中3例部分缓解，4例疾病稳定，17例疾病进展；治疗有效率为125%，疾病控制率为29.2%；中位生存期为5.7个月，6个月生存率为33%，9个月生存率为27%。治疗期间所有患者均未出现 3～4级不良反应。 结论： DC-CIK细胞治疗局部晚期和晚期胰腺癌患者安全可行，可改善患者免疫功能并产生临床获益。

Objective: To investigate the safety and efficiency of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cells in the treatment of local advanced and advanced pancreatic cancer. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 24 pancreatic cancer patients in Ⅲ-Ⅳ stage from the department of tumor bio-therapy of No.81 Hospital of PLA during Jul. 2011 to May. 2012 and were cultured in vitro to obtain DC and CIK cells. DCs were sensitized by PANC1 (pancreatic cancer cell line) cell lysates and then transfused to pancreatic cancer patients combined with CIK cells. The changes in peripheral blood lymphocyte subsets, serum tumor markers and clinical efficiency were evaluated before and after DC-CIK cell treatment. Results: The proportions of CD3+ T cells, CD8+T cells and CD4+CD25+Treg were significantly decreased after DC-CIK cell treatment for 3 months (all P<0.05), while the ratio of CD4+/CD8+ cells was significantly increased (1.1±0.7 vs 1.5±0.9, P<0.05). The serum tumor marker CA19-9 level declined 1 month after-treatment (382.8±277.7 vs 213.8±214.6, P<0.05) and 3 months after-treatment (2138±214.6 vs 1540±118.2, P<0.01). In all the 24 patients, there was no case of complete response, 3 cases of partial response, 4 cases of stable disease, 17 cases of progressive disease; the clinical response rate was 12.5% and the disease control rate was 29.2%; the median survival time was 5.7 months; the 6- and 9-month overall survival rates were 33% and 27%, respectively. No grade 3-4 adverse events were observed in all cases during treatment. Conclusion: DCs combined with CIK cell treatment on local advanced and advanced pancreatic cancer patients are safe and feasible. DC-CIK treatment could increase patient's immune function and show clinical benefits.

中国人民解放军南京军区医学科技创新基金（No. 08MB055）