外周血PD-1及相关免疫指标在鼻咽癌患者放化疗过程中的变化及其意义

Changes and significance of peripheral blood PD-1 level and related immune indicators during radiochemotherapy in patients with nasopharyngeal carcinoma

目的:检测鼻咽癌患者接受放化疗过程中T细胞表面PD-1表达、T细胞亚群等免疫指标的水平,探讨不同治疗时间段内患者的免疫功能。方法:收集2015年4月至2015年9月在福建省肿瘤医院经病理确诊的30例鼻咽癌患者的血液标本,通过流式细胞术动态监测患者在不同治疗时段(治疗前、新辅助化疗后、放疗结束)的免疫指标水平,包括T细胞上PD-1及T细胞亚群、NK细胞、B细胞等。结果:与治疗前相比,新辅助化疗后外周血CD3^(+)细胞、CD4^(+)T细胞、CD8^(+)CD28^(+)T细胞及CD4^(+)/CD8^(+)比值显著升高,而CD19(^(+)即B细胞)及CD3-CD16^(+)CD56(^(+)即NK细胞)细胞水平显著下降(均P<0.05)。放化疗结束后,外周血CD4^(+)细胞、CD8^(+)CD28^(+)T细胞、CD4^(+)/CD8^(+)比值下调至较治疗前更低的水平(均P<0.05),而NK细胞的比例则表现为上调(P<0.05)。与治疗前相比,放疗后T细胞PD-1的表达水平显著升高(P<0.05)。结论:鼻咽癌患者外周血T细胞亚群比例在新辅助化疗后上调,而放疗结束时明显下降,提示放疗结束时患者的免疫功能受到显著抑制;T细胞PD-1的表达水平在放疗结束时显著上调,意味着放化疗结束时可能正是使用PD-1抑制剂的良机,抗PD-1维持治疗有望产生更高效持久的抗肿瘤效应。

Objective:To detect the expression of programmed death molecule 1(PD-1)on T cell surface,the levels of T cell subsets and other immune indices in patients with nasopharyngeal carcinoma(NPC)during chemoradiotherapy,and to discuss the immune function of patients in different treatment periods.Methods:Blood samples of 30 patients who were pathologically confirmed of nasopharyngeal carcinoma in Fujian Cancer Hospital from April 2015 to September 2015 were collected for this study.Flow cytometry was used to dynamically detect the immune indicators of NPC patients in different treatment periods(pre-treatment,post-chemotherapy and post-radiotherapy),including PD-1 on T cell surface,T cell subsets,NK cells and B cells etc.Results:Compared with pretreatment,the proportion of CD3^(+)T cells,CD4^(+)T cells,CD8^(+)CD28^(+)T cells and CD4^(+)/CD8^(+)ratio in peripheral blood of patients increased significantly,while the proportion of B cells(CD19^(+))and NK cells(CD3-CD16^(+)CD56^(+)cells)decreased significantly after neoadjuvant chemotherapy(all P<0.05).After chemoradiotherapy,the proportion of CD4^(+)T cells,CD8^(+)CD28^(+)T cells and CD4^(+)/CD8^(+)ratio in peripheral blood of patients decreased to a lower level compared to pre-treatment(all P<0.05),while the proportion of NK cells was up-regulated(P<0.05).Compared with pre-treatment,the expression level of PD-1 on T cells increased significantly after radiotherapy(P<0.05).Conclusion:The study found that the proportion of T cell subsets in peripheral blood increased after neoadjuvant chemotherapy but decreased significantly at the end of radiotherapy,indicating that the immune function of NPC patients was significantly suppressed at the end of radiotherapy.The expression level of PD-1 on T cells was significantly up-regulated after radiotherapy,indicating that the end of chemoradiotherapy maybe an optimal timepoint for anti-PD-1 immunotherapy,which may exert more efficient and long-lasting anti-tumor effect for NPC.