[关键词]
[摘要]
目的:对比幽门螺杆菌(Helicobacter pylori,Hp)感染阴性和阳性的晚期胃癌患者接受自体树突状细胞联合细胞因子诱导的杀伤(dendritic cells-cytokine induced killer,DC-CIK)细胞维持治疗的疗效差异。方法:收集2010年6月至2012年6月中国人民解放军第174医院肿瘤中心收治的72例晚期胃癌患者,年龄29~90岁,中位年龄56岁,通过胃镜检查进行胃癌确诊并检测Hp,分为Hp阳性组(45例)及Hp阴性组(27例),在接受手术或/和放化疗后,接受2疗程自体DC-CIK维持治疗,比较两组外周血培养的DC分化成熟情况及临床疗效差异。结果: 两组DC成熟过程形态变化无差异;Hp阳性组DC表面分子CD83、CD86表达显著高于Hp阴性组(P<0.01),两组间HIA-DR表达无明显差异(P>0.05)。Hp阳性组治疗后生活质量评分(KPS)、外周血T细胞亚群(CD3+、CD4+、CD8+)比例较治疗前显著提高(P<0.05),肿瘤标志物(CEA、CA199、CA724)表达较治疗前下降(P<0.05)。Hp阴性组治疗后肿瘤标志物表达、外周血T淋巴细胞比例较治疗前显著降低(P<005),KPS评分较治疗前无明显变化(P>0.05)。Hp阳性组治疗后KPS评分、CEA和CA199表达以及CD3+和CD4+T细胞数量等的改善均优于Hp阴性组(P<0.05),但瘤体稳定率、CA724、CD8+T细胞比例无显著差异(P>0.05)。共随访2年,阳性组患者中位生存期为12.64个月,长于阴性组的11.42个月(P<0.05)。结论: 携带Hp抗原信息的DC疫苗协同CIK治疗能够提高Hp感染的晚期胃癌患者的自身免疫功能,达到稳定瘤体、改善生活质量、延长生存期的目的。
[Key word]
[Abstract]
Objective: To evaluate the effect of Helicobacter pylori (Hp) infection on the outcome of maintenance therapy with autologous dendritic cells-cytokine induced killer (DC-CIK) cells in gastric cancer patients. Methods: Seventy-two patients with advanced gastric cancer, aged 29-90 years, who were admitted to the Department of Oncology of No. 174 Hospital of PLA between June, 2010 and June, 2012 were included in this study. Based on the gastroscopic findings, patients were divided into two groups: Hp-positive and Hp-negative. Both groups received two courses of autologous DC-CIK immunotherapy after surgery or radiotherapy and chemotherapy. At the end of treatment, DC differentiation and maturation, treatment efficacy and patients outcomes in the two groups were analyzed. Results: No significant difference was observed in the morphology and maturation status of DCs between two groups (P>0.05). Levels of CD83 and CD86 on the surface of DCs were significantly higher in the Hp-positive group than those in the Hp-negative group (P<0.01), but surface levels of HLA-DR in DCs had no significant difference between two groups (P>0.05). In the Hp-positive group, the quality of life KPS score and levels of T lymphocyte markers (CD3+, CD4+ and CD8+) were significantly increased (P<0.05) but levels of tumor markers CEA, CA199 and CA724 were significantly decreased (P<0.05) after treatment. In the Hp-negative group, levels of tumor markers and the T lymphocyte markers were significantly different before and after treatment (P<0.05), but the KPS score was not significantly improved (P>0.05). Hp-positive patients had better KPS score, higher levels of CEA and CA199, and more abundant CD3+ CD4+T cells than Hp-negative patients (P<0.05). In contrast, the two groups did not significantly differ in tumor stability, CA724 expression, and the number of CD8+T cells (P>0.05). At the end of 2-years follow-up, the median survival time was 12.64 months in the HP-positive group and 11.42 months in the HP-negative group (P<0.05). Conclusion: Hp infection may help stabilize the tumor size, improve the quality of life, and prolong the survival time in patients with advanced gastric cancer undergoing maintenance therapy with DC-CIK cells.
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[基金项目]
南京军区医学科技创新课题资助(No.10MA068);厦门市科技计划创新项目资助(No.3502z20134026,No.3502z20144034)。