Zhao Peng, Bu Xiaocui, Wei Xiaofang, Sun Weihong, Xie Xihe, Li Changyou, Guo Qingming, Zhu Danni, Wei Xiaoqiang, Gao Daiqing
Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
The Affiliated Cardiovascular Hospital, Medical College of Qingdao University, Qingdao 266071, China.
Int Immunopharmacol. 2015 Apr;25(2):450-6. doi: 10.1016/j.intimp.2015.02.010. Epub 2015 Feb 16.
Dendritic cell (DC) vaccination and cytokine-induced killer (CIK) cell therapy (DC/CIK) have shown limited success in the treatment of advanced non-small cell lung cancer (NSCLC). To investigate the reason for this limited success, the effects of DC/CIK cell therapy on the immune responses of tumor-bearing patients and patients with resected NSCLC were evaluated. In the total 50 patients studied, the serum concentrations of the Th2 cytokines (IL-4 and IL-10) in tumor-bearing patients were significantly higher than those with resected NSCLC before immunotherapy. The post-therapy Th1 cytokine (IFN-γ) level in patients with resected NSCLC significantly increased from the pre-therapy level. In contrast, significantly enhanced post-therapy Th2 cytokine (IL-4 and IL-10) levels were found in tumor-bearing patients. The intracellular staining assay revealed that DC/CIK cell therapy increased the IFN-γ-producing T lymphocyte (CD8(+)IFN-γ(+)) frequency in patients with resected NSCLC, but these lymphocytes were not found in tumor-bearing patients. Furthermore, overproduction of vascular endothelial growth factor (VEGF) in tumor-bearing patients showed a statistically positive correlation with IL-4, suggesting that VEGF might be responsible for the predominance of serum Th2 cytokines. In a word, tumor-bearing patients developed a Th2-dominant status that could not be reversed toward Th1 following immunotherapy. A combined regiment of DC vaccination and CIK cell therapy with other treatments to overcome systemic Th2-dominant immune response might improve the current clinical benefit.
树突状细胞（DC）疫苗接种和细胞因子诱导的杀伤（CIK）细胞疗法（DC/CIK）在晚期非小细胞肺癌（NSCLC）的治疗中取得的成功有限。为了探究成功有限的原因，评估了DC/CIK细胞疗法对荷瘤患者和非小细胞肺癌切除患者免疫反应的影响。在总共50例研究患者中，荷瘤患者的Th2细胞因子（IL-4和IL-10）血清浓度在免疫治疗前显著高于非小细胞肺癌切除患者。非小细胞肺癌切除患者治疗后的Th1细胞因子（IFN-γ）水平较治疗前显著升高。相比之下，荷瘤患者治疗后Th2细胞因子（IL-4和IL-10）水平显著升高。细胞内染色分析显示，DC/CIK细胞疗法增加了非小细胞肺癌切除患者中产生IFN-γ的T淋巴细胞（CD8(+)IFN-γ(+)）频率，但在荷瘤患者中未发现这些淋巴细胞。此外，荷瘤患者中血管内皮生长因子（VEGF）的过量产生与IL-4呈统计学正相关，表明VEGF可能是血清Th2细胞因子占优势的原因。总之，荷瘤患者形成了以Th2为主的状态，免疫治疗后无法向Th1逆转。联合DC疫苗接种和CIK细胞疗法与其他治疗方法以克服全身性Th2为主的免疫反应可能会改善当前的临床疗效。
