[关键词]
[摘要]
目的:探讨结肠癌患者完整结肠系膜切除(complete mesocolic excision,CME)术后化疗联合DC-CIK细胞免疫治疗的临床疗效和安全性。方法:收集2012年6月至2013年12月河北省沧州中西医结合医院肿瘤外科的82例Ⅲ期结肠癌患者,随机分为两组,均接受CME手术。单纯化疗组(n=42)采用CapeOX方案,给予6周期化疗;DC-CIK细胞免疫治疗联合化疗组(联合治疗组,n=40)除采用CapeOX方案化疗外,同时给予负载自身肿瘤抗原的DC肿瘤疫苗和细胞因子诱导的杀伤细胞(CIK)进行细胞免疫治疗。观察两组患者治疗前后CEA的变化、细胞免疫指标(外周血CD3+、CD4+、CD8+、CD19+、CD56+及CD4+CD25+FOXP3+Treg细胞的百分比)、治疗期间的药物毒副作用以〖JP2〗及比较两组2年肿瘤复发率。结果: 两组患者术后2周CEA数值较术前均有明显下降(P<0.05)。两组患者治疗前、后及术后1年的CEA数值差异无统计学意义(P>005)。单纯化疗组术后2年的CEA数值与治疗后及与联合治疗组相比均明显升高(均P<0.05)。单纯化疗组化疗后CD8+和Treg细胞的百分比明显下降(P<0.05),余指标变化无统计学意义。联合治疗组治疗后CD3+、CD4+、CD8+、CD19+、CD3+CD56+细胞的百分比显著提高(P<0.05),Treg细胞的百分比明显下降(P<0.05)。联合治疗组患者的骨髓抑制、恶心呕吐、腹泻、外周神经毒性及手足综合征等药物毒副作用的发生率均明显降低(均P<0.05)。单纯化疗组的2年肿瘤复发率为2381%,联合治疗组为7.5%,差异有统计学意义(P<0.05)。结论: DC-CIK细胞免疫治疗联合化疗可以提高结肠癌患者术后的机体免疫功能,改善生活质量,减少化疗药物的毒副作用,并明显降低肿瘤2年的复发率。
[Key word]
[Abstract]
Objective:To evaluate the safety and clinical effects of chemotherapy combined with dendritic cells and cytokine-induced killer cells (DC-CIKs) in the treatment of colon cancer patients after complete mesocolic excision (CME). Methods: The present study enrolled 82 patients with colon cancer (stageⅢ) who underwent CME in the Department of Surgery, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province between June 2012 and December 2013. The patients were randomly divided into chemotherapy group and combined therapeutic group. Chemotherapy group consisted of 42 cases, who received 6 cycles of chemotherapy with the protocol of CapeOX. Combined therapeutic group consisted of 40 cases, who were given DC loaded with autologous tumor antigen and autologous CIK cells, in addition to the same chemotherapeutical protocol. The changes in carcino-embryonic antigen (CEA), cellular immune indicators (percentage of CD3+, CD4+, CD8+, CD19+, CD56+, and CD4+ CD25+ FOXP3+ Treg in peripheral blood) and side effects of drugs were recorded, and the 2-year recurrence rate of both groups were compared. Results:The values of CEA decreased significantly at 2 weeks after the procedures in both groups (P<0.05). There were no differences in the values of CEA before and after the treatment as well as 1 year after surgery in both groups (P>0.05). The values of CEA at 2 years after surgery in chemotherapy group were notably higher than those of post-treatment and those of combined therapeutic group (both P<0.05). The proportion of CD8+ and Tregs was reduced significantly after the treatment in chemotherapy group (P<0.05), and other indicators showed no significant differences. The proportion of CD3+, CD4+, CD8+, CD19+ and CD3+CD56+ was increased markedly (P<0.05), whereas the proportion of Tregs was reduced significantly after the treatment in the combined therapeutic group (P<0.05). Fewer side effects (including bone marrow suppression, nausea and vomiting, diarrhea, peripheral nerve toxicity and hand-foot syndrome) were observed in the combined therapeutic group, as compared with the chemotherapy group (all P<0.05). The 2-year recurrence rates in the chemotherapy group and the combined therapeutic group were 23.81% and 7.5%, respectively, with significant difference between two groups (P<0.05). Conclusion: Sequential DC injection and autologous CIK cells transfusion combined with chemotherapy may improve the therapeutic effect in colon cancer patients with CME surgery by enhancing the autoimmune function. Therefore, it can improve the life quality, reduce side effects caused by drugs and more importantly, reduce the 2-year recurrence rate.
[中图分类号]
[基金项目]
河北省卫生厅青年科技基金资助项目(No. 1020140135);沧州市科技支撑计划资助项目(No. 131302194)