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树突状细胞激活的细胞因子诱导的杀伤细胞增强了化疗对非小细胞肺癌患者术后的抗肿瘤作用。

Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery.

机构信息

Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

出版信息

Cytotherapy. 2009;11(8):1076-83. doi: 10.3109/14653240903121252.

DOI:10.3109/14653240903121252
PMID:19929470
Abstract

BACKGROUND AIMS

Cytokine-induced killer (CIK) cells have shown cytolytic activity against several tumor cells in vitro and in animal tumor models. Furthermore, CIK cells activated by dendritic cell (DC) stimulation show increased anti-tumor activity. This study aimed to evaluate the clinical efficacy of DC-activated CIK cell treatment following regular chemotherapy and the effects of this therapy on immune responses in patients with non-small cell lung cancer (NSCLC) after surgery.

METHODS

A paired study, with 42 patients in each group with stage I-IIIa NSCLC after surgery, was performed. Patients received chemotherapy alone (CT) or chemotherapy and DC-activated CIK cell treatment (immuno-CT). Disease-free survival (DFS) and overall survival were evaluated. CIK cell cytotoxicity against tumor cells was detected using a lactate dehydrogenase-based method. Serum cytokine levels in the immuno-CT group were detected using cytokine antibody arrays.

RESULTS

The cytotoxicity of CIK cells was significantly enhanced by DC activation. The 2-year overall survival rate in the immuno-CT group was significantly improved compared with the CT group (94.7 +/- 3.6% versus 78.8 +/- 7.0%, P < 0.05). The 2-year DFS of these two groups showed no significant difference. DC-activated CIK cell treatment increased production of cytokines that have known anti-tumor effects, including IFN-gamma, MIG, TNF-alpha and TNF-beta, in patients who had no progression, but they were not found in patients who developed recurrence/metastasis.

CONCLUSIONS

This study suggests that the role of DC-activated CIK cells in improvement of chemotherapy for malignant tumor treatment is associated with up-regulation of the production of cytokines involved in the anti-tumor effect.

摘要

背景与目的

细胞因子诱导的杀伤(CIK)细胞在体外和动物肿瘤模型中对多种肿瘤细胞显示出细胞溶解活性。此外,经树突状细胞(DC)刺激激活的 CIK 细胞显示出增强的抗肿瘤活性。本研究旨在评估 DC 激活的 CIK 细胞治疗在常规化疗后的临床疗效,以及该治疗对手术后非小细胞肺癌(NSCLC)患者免疫反应的影响。

方法

进行了一项配对研究,每组 42 例手术后 I-IIIa 期 NSCLC 患者。患者接受单独化疗(CT)或化疗加 DC 激活的 CIK 细胞治疗(免疫-CT)。评估无病生存期(DFS)和总生存期。采用乳酸脱氢酶法检测 CIK 细胞对肿瘤细胞的细胞毒性。采用细胞因子抗体阵列检测免疫-CT 组血清细胞因子水平。

结果

DC 激活显著增强了 CIK 细胞的细胞毒性。免疫-CT 组的 2 年总生存率明显高于 CT 组(94.7%±3.6%比 78.8%±7.0%,P<0.05)。两组的 2 年 DFS 无显著差异。DC 激活的 CIK 细胞治疗增加了无进展患者中具有已知抗肿瘤作用的细胞因子的产生,包括 IFN-γ、MIG、TNF-α和 TNF-β,但在发生复发/转移的患者中未发现。

结论

本研究表明,DC 激活的 CIK 细胞在改善恶性肿瘤化疗中的作用与参与抗肿瘤作用的细胞因子产生的上调有关。

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