Changes in Dendritic Cells of Peripheral Blood in 74 Lung Cancer Patients before and after GVAX Treatment and Their Clinical Significance
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摘要:
目的 探讨粒-巨噬细胞集落刺激因子（granulocyte-macrophage colony 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（PDC1=0.786，PDC2=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，其对预后的影响可能与患者外周血Treg比例有一定的相关性。 -
关键词:
- 肺癌 /
- 树突状细胞 /
- 调节性T细胞 /
- 粒-巨噬细胞集落刺激因子 /
- 预后
Abstract: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. -
Key words:
- Lung cancer /
- Dendritic cells (DCs) /
- Regulatory T cell /
- GM-CSF /
- Prognosis
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图 1 NSE正常组与升高组中DC1与DC2比例
A：GVAX治疗前，NSE升高组与正常组中DC1值；B：GVAX治疗后，NSE升高组与正常组中DC1值；C：GVAX治疗前后，NSE升高组与正常组中DC1变化值；D：GVAX治疗前，NSE升高组与正常组中DC2值；E：GVAX治疗后，NSE升高组与正常组中DC2值；F：GVAX治疗前后，NSE升高组与正常组中DC2变化值；1：NSE升高组；2：NSE正常组
Figure 1. Distribution of DC1 and DC2 in the normal and high-level NSE groups
图 2 早期肺癌患者治疗后DC2不同比例组的生存曲线
Figure 2. The survival curves of early lung cancer patients with different proportion of DC2 after GVAX therapy
图 3 晚期肺癌患者治疗后DC2不同比例组的生存曲线
Figure 3. The survival curves of advanced lung cancer patients with different proportion of DC2 after GVAX therapy
表 1 GVAX治疗前后肺癌患者外周血DC细胞分布
x±s，% Table 1. Distribution of DCs before and after GVAX vaccination in the different groups
x±s, % 
表 2 DC与GVAX治疗前实验室检测指标相关性
Table 2. Correlation between DC and indices tested in the laboratory before GVAX treatment
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