鼻咽癌患者外周血共刺激分子的表达水平及其临床意义

Expression level of costimulatory molecules in peripheral blood of the patients with nasopharyngeal carcinoma and its clinical significance

目的:检测鼻咽癌患者外周血中T细胞表面程序性死亡分子1(programmed death-1,PD-1)、刺激分子4-1BB的表达水平,探讨其在鼻咽癌中的临床意义。方法:选取2016年10至11月福建省肿瘤医院病理确诊的鼻咽癌患者30例作为研究对象,并选取同期本院体检中心性别、年龄相近的健康体检者30例作为对照组。通过流式细胞术检测外周血T细胞表面PD-1、4-1BB的表达情况以及T淋巴细胞亚群的比例。核磁共振扫描测量原发肿瘤体积。结果:鼻咽癌Ⅲ期患者外周血CD8+T细胞比例明显低于Ⅳ期患者[(13.1±6.2)%vs(18.7±5.5)%,P<0.05]。与对照组相比,CD4+T细胞上PD-1阳性表达率显著上调[(8.7±6.5)%vs(3.87±3.0)%,P<0.05]。鼻咽癌患者外周血T细胞PD-1、4-1BB分子表达水平与临床分期、肿瘤负荷、性别及年龄无显著相关(P>0.05)。结论:鼻咽癌患者外周血PD-1和4-1BB两种共刺激分子在患者体内肿瘤免疫逃逸中可能存在协同效应。联合干预这两种共刺激分子的信号通路可能具有更高效持久的抗肿瘤效应,可为鼻咽癌免疫治疗提供新的思路。

Objective ：To test expression levels of programmed death-1（PD-1） and costimulatory 4-1BB molecules on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma and to explore their clinical significance in immunotherapy of the patients with nasopharyngeal carcinoma. Methods： Thirty patients with nasopharyngeal carcinoma who were pathological diagnosed and hospitalized in Cancer Hospital of Fujian Province during October to November 2016 were selected as objects of the research, and 30 healthy individuals who are similar to the research objects in gender and age and took physical examination in a medical examination center of the same hospital during the same period as a control group. Expressions of PD-1 and 4-1BB on surface of T cells in peripheral blood as well as ratio of T lymphocyte subgroups were detected by a flow cytometry as-say. Using nuclear magnetic resonance scanning, volumes of the primary carcinoma were measured. Results： Ratio of CD8 ＋ T cell in peripheral blood of the patients with Ⅲ stage of nasopharyngeal carcinoma was obviously lower than that of the patients with Ⅳ stage of nasopharyneal carcinoma （[13.1 ± 6.2]% vs [18.7 ±5.5]%,P〈0.05）.Comparing with the control group, positive expression rate of PD-1 on CD4 ＋ T cell in the research group was significantly up-regulated（[8.7 ± 6.5]% vs [3.87 ± 3.0] %, P〈0.05）. Expression levels of PD-1 and 4-1BB on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma did not obviously correlated with clinical staging, tumor load, gender and age of the patient （P〉0.05）. Conclusion： There could be a synergistic effect between the two costimulatory molecules, PD-1 and 4-1BB, in an immune escape process of tumor. Joint intervening a signaling pathway of these two costimulation molecules might have more effective and durable antitumor effects,which might provide a novel ideal for an immunotherapy of the nasopharyngeal carcinoma.