74例肺癌患者GVAX治疗前后外周血树突状细胞变化及其临床意义

Changes in Dendritic Cells of Peripheral Blood in 74 Lung Cancer Patients before and after GVAX Treatment and Their Clinical Significance

目的:探讨粒-巨噬细胞集落刺激因子(granulocyte-macrophage colonv stimulating factor,GM-CSF)基因修饰的肿瘤细胞疫苗治疗前后肺癌患者外周血中DC两个不同亚群(DC1,DC2)的比例、治疗前后比例变化与临床病理特征的相关性及对生存的影响。方法:对74例接受GM-CSF基因修饰的肿瘤细胞疫苗(GM-CSF modified tumor cell vaccine,GVAX)治疗的肺癌患者,采用流式细胞技术检测患者治疗前后外周血DC及淋巴细胞亚群的比例,分析治疗前后DC比例的变化、治疗前后DC比例与治疗前血清标志物及免疫细胞的关系、治疗前后DC比例对肺癌患者生存的影响。结果:接受GVAX疫苗治疗后外周血DC1与DC2比例无明显变化(P_(DC1)=0.786,P_(DC2)=0.779);神经烯醇化酶(NSE)水平升高组中的DC亚群比例高于NSE水平正常组;治疗后DC2比例与治疗前Treg呈负相关;对于早期肺癌患者,治疗后DC2比例低于均值者的生存时间比高于均值者的生存时间明显延长。结论:治疗后DC2比例可作为早期患者GVAX疫苗疗效及判断预后的免疫指标。

Objective： Dendritic cells （ DC ） can be divided into two subgroups based on the markers and functions： myeloid-DC （ DC1 ） and plasmacytoid-DC （ DC2 ）. This study evaluated the clinical significance of the proportion of DC subgroups in the peripheral blood of lung cancer patients before and after GVAX vaccineation. Methods： Seventy-four patients with lung cancer were enrolled in the study. Flow cytometry was used to detect the proportion of DCs and lymphocyte subgroups before and after GVAX vaccination. The correlation of DCs with serum markers and immune cells was tested. The Kaplan-Meier was used to analyze the correlations between DCs and survival of patients. Results： There was no significant change in the proportion of DCs after GVAX vaccination. The proportion of DCs was higher in the group with elevated levels of neuron-specific enolase （ NSE ） than in normal controls. A negative correlation was observed between the proportion of DC2 post-GVAX vaccination and the proportion of Treg pre-GVAX vaccination. For patients with early lung cancer, those with a proportion of DC2 below the mean value after vaccination had better overall survival compared with those with a proportion of DC2 greater than the mean value. Conclusion： A low proportion of DC2 after GVAX vaccination is a predictor of better prognosis for patients who received GVAX vaccination. DC2 proportion post-GVAX vaccination may have a correlation with the proportion of Treg in the peripheral blood pre-GVAX vaccination.