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[摘要]
目的:回顾性分析自体DC联合CIK(DC-CIK)细胞治疗96例胃癌患者的临床疗效和安全性。方法:采集2011年8月至2016年4月解放军第86医院肿瘤科及解放军第81医院肿瘤生物治疗中心收治的96例胃癌患者的外周血单核细胞 (peripheral blood mononuclear cell, PBMC),经实验室体外诱导培养DC和CIK细胞,DC通过胃癌MGC-803细胞裂解物致敏后与CIK细胞回输给患者,观察DC-CIK细胞治疗胃癌患者的临床疗效和安全性。结果:96例胃癌患者经DC-CIK细胞免疫治疗后,客观反应率为15.6%,疾病控制率为55.2%;1年生存率为56.0%,36~56个月总生存率维持在37.0%。免疫细胞治疗前后患者外周血肿瘤标志物CEA、CA199和CA724值均无明显变化。细胞治疗后患者外周血CD4+CD25+细胞比例显著下降\[(3.22±1.20)% vs (2.46±1.04)%,P<0.01\],CD3+、CD4+、CD8+、CD3+CD56+细胞百分比及CD4+/CD8+比值均无显著变化(P>0.05)。单因素分析显示,TNM分期、细胞治疗次数、治疗前CEA和CA199值为DC-CIK治疗胃癌预后的影响因素(P<0.05);多因素分析显示,细胞治疗次数、治疗前CEA和CA199值与DC-CIK细胞治疗胃癌患者的预后相关(P<005)。结论:DC-CIK细胞免疫治疗对于胃癌患者是一种安全有效的治疗方式,多次治疗可能提高患者远期生存率。
[Key word]
[Abstract]
Objective:To retrospectively analyze safety and clinical efficacy of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cellular immunotherapy in treatment of the 96 patients with gastric cancer (GC). Methods: Peripheral blood mononuclear cells (PBMCs) from the 96 GC patients who were hospitalized in the Oncology Department of the 86th Hospital of PLA and Tumor Biotherapy Center of the 81st Hospital of PLA during August 2011 to April 2016 were collected and cultured ex vivo to obtain DC and CIK cells. After sensitization with gastric cancer MGC-803 line cell lysates, the DCs combined with CIK cells were transfused back to the GC patients. Clinical efficacy and safety of the DC-CIK cellular immunotherapy were observed. Results: Overall response rate and disease control rate of the 96 GC patients following the DC-CIK immunotherapy were 15.6% and 55.2% respectively. Their 1 year survival rate was 56.0%, whereas rate of overall survival for 36-56 months was maintained at about 37.0%. No significant difference was observed in peripheral blood value of tumor markers, CEA, CA199 and CA724 of the GC patients between pretherapy and postherapy. After the DC-CIK immunotherapy the percentage of CD4+CD25+ Treg cell in peripheral blood of the GC patients was significantly decreased (\[3.22±1.20\]% vs \[2.46±1.04\]%, P<0.01), but the percentages of CD3+, CD4+, CD8+ and CD3+CD56+ T cell subsets as well as ratio of CD4+/CD8+ did not show any significant changes (P>0.05). Kaplan-Meier univariate analysis showed that TEM staging, times of the cellular immunotherapy as well as pretherapy value of CEA and CA199 were influence factors for prognosis of the GC patients treated with the DC-CIK cellular immunotherapy. Multivariate analysis with Cox model further indicated that times of the cellular immunotherapy as well as pretherapy value of CEA and CA199 were significantly associated with prognosis of the GC patients treated with the DC-CIK cellular immunotherapy (P<0.05). Conclusion: Autologous DC-CIK immunotherapy might be a safe and efficacy therapy approach for the GC patients, however multiple therapy of the DC-CIK immunotherapy could improve long-term survival rate of the patients with GC.
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[基金项目]
南京军区面上课题基金资助 (No.15ms 077)