鼻咽癌放化疗治疗患者外周血PD-1及免疫指标水平的变化及其临床意义

Significance of changes of PD-1 and immune indexes in peripheral blood of patients with nasopharyngeal carcinoma treated with radiotherapy and chemotherapy

目的探讨鼻咽癌放化疗治疗患者外周血程序性死亡受体1(PD-1)及免疫指标水平的变化及其临床意义。方法回顾性选取2020年1月至2023年江苏省肿瘤医院收治的90例鼻咽癌患者,所有患者均经病理确诊并接受放化疗治疗,采集其血液样本之后采用流式细胞术对不同时间段(治疗前、新辅助化疗后、放疗后)外周血淋巴细胞亚群比例、外周血PD-1、CD8^(+)CD28^(+)细胞比例的水平变化予以动态监测并比较。结果鼻咽癌患者新辅助化疗后CD3^(+)、CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值分别为(72.28±8.37)%、(39.27±8.58)%、1.58±0.67,均明显高于治疗前,CD3-CD16^(+)CD56^(+)、CD19^(+)细胞比例分别为(18.27±8.38)%、(7.87±4.08)%,均明显低于治疗前,差异均有统计学意义(P<0.05);新辅助化疗后与治疗前的CD8^(+)细胞比例比较,差异无统计学意义(P>0.05)。鼻咽癌患者新辅助化疗之后CD8^(+)CD28^(+)细胞比例为(10.68±3.87)%,明显高于治疗前,差异有统计学意义(P<0.05);新辅助化疗后与治疗前的外周血PD-1水平比较,差异无统计学意义(P>0.05)。放疗后与治疗前的CD3^(+)细胞比例比较,差异无统计学意义(P>0.05);鼻咽癌患者放疗后CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值、CD19^(+)细胞比例分别为(26.68±6.09)%、0.88±0.29、(3.69±2.36)%,均明显低于治疗前,CD8^(+)、CD3-CD16^(+)CD56^(+)细胞比例分别为(31.03±8.08)%、(27.39±10.26)%,均明显高于治疗前,差异均有统计学意义(P<0.05)。鼻咽癌患者放疗后CD8^(+)CD28^(+)细胞比例为(7.08±2.57)%,明显低于治疗前,外周血PD-1水平为(13.38±6.27)%,明显高于治疗前,差异均有统计学意义(P<0.05)。结论新辅助化疗之后鼻咽癌患者外周血T细胞亚群比值处于持续上调趋势,而放疗完成后处于下降趋势,表明鼻咽癌患者于放疗完成后免疫功能受损;放疗完成后鼻咽癌患者T细胞PD-1表达水平明显上调,提示PD-1抑制剂最佳使用时间可能为放化疗完成时,抗PD-1维持治疗可发挥持久、高效的抗肿瘤作用。

Objective To study the changes of progrommed death-1(PD-1)and immune indexes in peripheral blood of patients with nasopharyngeal carcinoma treated with radiotherapy and chemotherapy.Methods A total of 90 patients with nasopharyngeal carcinoma admitted to Jiangsu Cancer Hospital from January 2020 to 2023 were retrospectively selected.All patients were pathologically confirmed and received radiotherapy and chemotherapy treatment.After collecting blood samples,flow cytometry was used to dynamically monitor and compare the changes of the proportion of peripheral blood lymphocyte subsets,peripheral blood PD-1,CD8^(+)CD28^(+)cells.in peripheral blood at different time periods(before chemoradiotherapy,after neoadjuvant chemotherapy and after radiotherapy).Results After neoadjuvant chemotherapy,the proportions of CD3^(+),CD4^(+)cells,CD4^(+)/CD8^(+)ratio in nasopharyngeal carcinoma patients were(72.28±8.37)%,(39.27±8.58)%,and 1.58±0.67,respectively,which were significantly higher than those before treatment,The proportions of CD3-CD16^(+)CD56^(+)and CD19^(+)cells were(18.27±8.38)%and(7.87±4.08)%,respectively,which were significantly lower than those before treatment,and the differences were statistically significant(P<0.05);there was no statistically significant difference in the proportion of CD8^(+)cells between after neoadjuvant chemotherapy and before treatment(P>0.05).The proportion of CD8^(+)CD28^(+)cells in nasopharyngeal carcinoma patients after neoadjuvant chemotherapy was(10.68±3.87)%,which was significantly higher than that before treatment,and the difference was statistically significant(P<0.05);there was no statistically significant difference in the peripheral blood PD-1 levels after neoadjuvant chemotherapy compared to before treatment(P>0.05).There was no statistically significant difference in the proportion of CD3^(+)cells between after radiotherapy and before treatment(P>0.05);the proportion of CD4^(+)cells,CD4^(+)/CD8^(+)ratio,the proportion of CD19^(+)cells in nasopharyngeal carcinoma patients after radiotherapy was(26.68±6.09)%,0.88±0.29,and(3.69±2.36)%,respectively,which were significantly lower than those before treatment,the proportions of CD8^(+)and CD3-CD16^(+)CD56^(+)cells were(31.03±8.08)%and(27.39±10.26)%,respectively,which were significantly higher than those before treatment,and the differences were statistically significant(P<0.05).Conclusion After neoadjuvant chemotherapy,the proportion of peripheral blood T cell subpopulations in nasopharyngeal carcinoma patients showed a continuous upward trend,while it showed a downward trend after radiotherapy,indicating that the immune function of nasopharyngeal carcinoma patients was impaired after radiotherapy.The expression level of PD-1 in T cells of nasopharyngeal carcinoma patients was significantly up-regulated after radiotherapy,suggesting that the best time to use PD-1 inhibitors may be when radiotherapy and chemotherapy are completed,and anti-PD-1 maintenance therapy can play a long-lasting and efficient anti-tumor effect.