摘要
目的探讨放化疗对鼻咽癌患者外周血髓源性抑制细胞（MDSC）和调节性T细胞（Treg）的影响，及其与放射性口腔黏膜炎的关系。方法选择2012年9月1日至2015年12月1日间进行放疗及同期放化疗的初治鼻咽癌患者60例，健康对照者20例。采用流式细胞术检测患者治疗前、放疗40 Gy、放疗结束和放疗后3个月外周血HLA－DR－CD11b＋CD33＋MDSC、CD4＋CD25＋CD127low/－Treg的水平。同时比较放疗结束时发生0～Ⅱ级和Ⅲ～Ⅳ级放射性口腔黏膜炎患者的HLA－DR－CD11b＋CD33＋MDSC和CD4＋CD25＋CD127low/－Treg水平。结果鼻咽癌患者治疗前、放疗40 Gy、放疗结束和放疗后3个月的外周血CD4＋CD25＋CD127low/－Treg水平分别为（8.42±1.52）%、（9.10±1.57）%、（8.87±1.56） %和（7.31±1.43）%，放疗40 Gy、放疗结束和放疗后3个月与治疗前比较，差异均有统计学意义（均P〈0.05）。治疗前Ⅰ～Ⅱ期和Ⅲ～Ⅳ期患者外周血CD4＋CD25＋CD127low/－Treg水平分别为（7.65±1.94）%和（8.63±1.39）%，差异有统计学意义（P＝0.042）。鼻咽癌患者治疗前、放疗40 Gy、放疗结束和放疗后3个月的外周血HLA－DR－CD11b＋CD33＋MDSC水平分别为（2.14±1.21）%、（4.08±1.90）%、（3.76±1.31）%和（1.52±0.88）%，放疗40 Gy、放疗后3个月与治疗前比较，差异有统计学意义（均P〈0.05）。Ⅰ～Ⅱ期和Ⅲ～Ⅳ期患者外周血HLA－DR－CD11b＋CD33＋MDSC水平分别为（1.35±0.66）%和（2.25±1.26）%，差异有统计学意义（P＝0.007）。放疗结束时，0～Ⅱ级和Ⅲ～Ⅳ级放射性口腔黏膜炎患者外周血HLA－DR－CD11b＋CD33＋MDSC水平分别为（3.15±1.04）%和（4.41±1.27）%，差异有统计学意义（P＝0.012）。0～Ⅱ级和Ⅲ～Ⅳ级放射性口腔黏膜炎患者外周血CD4＋CD25＋CD127low/－Treg水平分别为（8.41±1.52）%和（9.91±1.23）%，差异有统计学意义（P＝0.02）。
结论初治鼻咽癌患者外周血HLA－DR－CD11b＋CD33＋MDSC、CD4＋CD25＋CD127low/－Treg的水平高于健康对照者，且与鼻咽癌分期有关。鼻咽癌单纯放疗及同期放化疗过程中，HLA－DR－CD11b＋CD33＋MDSC和CD4＋CD25＋CD127low/－Treg水平明显增高，患者机体免疫能力下降，与治疗导致的放射性口腔黏膜炎有关。
ObjectiveTo investigate the percentage of myeloid-derived suppressor cells （MDSC） and T regulatory cells （Treg） in peripheral blood of nasopharyngeal cancer （NPC） patients undergoing concurrent chemoradiotherapy or radiotherapy alone.
MethodsSixty NPC patients who received radiotherapy or concurrent chemoradiotherapy from September 2012 to November 2015 and 20 healthy individuals were included in this study. For the patients, the blood samples were collected at four time points： pre-radiation （Pre-RT）, reaching a dose of 40 Gy （RT-40 Gy）, finishing radiation （RT-finish） and three months after finishing radiation （3m-post-RT）. Flow cytometry was used to evaluate the percentage of Treg （CD4＋ CD25＋ CD127low/-） and MDSC （HLA-DR-CD11b＋ CD33＋ ） cells in peripheral blood.
ResultsTreg and MDSC cells were present in peripheral blood lymphocytes of healthy individuals as a percentage of （7.50±1.62）% and （1.08±0.48）%, respectively. The proportions of peripheral Treg cells in patients at Pre-RT, RT-40 Gy, RT-finish and 3m-post-RT time points were （8.42± 1.52）%, （9.10±1.57）%, （8.87±1.56）% and （7.31±1.43）%, respectively, showing a statistically significant difference between Pre-RT and the other groups （P〈0.05）. At Pre-RT point, the percentage of Treg cells in Stage Ⅲ-Ⅳ patients [（8.63±1.39）%] was higher than that in Stage Ⅰ-Ⅱ [（7.65±1.94）%, P=0.042]. Moreover, the proportions of peripheral MDSC cells in patients at Pre-RT, RT-40 Gy, RT-finish and 3m-post-RT time points were （2.14±1.21）%, （4.08±1.90）%, （3.76±1.31）% and （1.52±0.88）%, respectively. The percentages of MDSC cells at RT-40 Gy and RT-finish points were significantly higher than those at Pre-RT, while the percentage of MDSC cells at 3m-post-RT was significantly lower than those at Pre-RT （P〈0.05）. At Pre-RT point, the percentage of MDSC cells in Stage Ⅲ-Ⅳ patients [（2.25±1.26）%] was higher than that in Stage Ⅰ-Ⅱ [（1.35±0.66）%, P=0.007]. At RT-finish point, the proportions of MDSC and Treg cells in patients with Ⅲ-Ⅳ grade of radiation induced oral mucositis [（4.41±1.27）% and （9.91±1.23）%] were significantly higher than those in Ⅰ-Ⅱ grade patients [（3.15±1.04）% and （8.41±1.52）%, both of P〈0.05].
ConclusionsThe proportions of MDSC and Treg cells in initial treated NPC patients are higher than healthy individuals, and they are also associated with the tumor stages. During the concurrent chemoradiotherapy and radiation, the percentage of MDSC and Treg cells is elevated, suggesting a decreased immune activity. The increase of MDSC and Treg cells is related to radiation induced oral mucositis.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2017年第8期579-583,共5页
Chinese Journal of Oncology
基金
扬州市科技局社会发展科技攻关计划（2012131）
江苏省苏北人民医院院课题（yzuems201412）
关键词
鼻咽肿瘤:调节性T细胞
髓源性抑制细胞
细胞免疫能力
放射性口腔黏膜炎
Nasopharyngeal neoplasms
T regulatory cells
Myeloid-derived suppressorcells
Immune activity
Radiation induced oral mucositis
