摘要
目的:探究环氧合酶2(COX-2)在食管鳞癌(ESCC)放疗前后的表达变化规律及其对免疫微环境的影响。方法:收集56例接受放疗的ESCC患者外周静脉血,检测放疗前后ESCC患者血清中COX-2、调节性T细胞(Treg)、细胞毒性T效应细胞(Teff)含量。构建ESCC的兔移植瘤模型并接受大分割/常规分割放疗,检测COX-2蛋白及其mRNA、Treg、Teff在ESCC移植瘤中的表达和浸润情况。结果:ESCC患者在放疗中、放疗后血清COX-2表达逐渐升高,较基线值均有明显差异(P=0.006,P<0.001)。ESCC患者在放疗中、放疗后外周血中CD3+CD8+细胞毒性Teff细胞比例较基线水平降低(P=0.070,P=0.003)。而外周血中CD4+CD25+Treg细胞在放疗中、放疗后比例较基线水平升高(P=0.030,P<0.001)。动物实验结果显示,接受大分割照射的移植瘤组织中COX-2 mRNA和蛋白水平无明显变化,接受常规分隔照射的COX-2 mRNA及蛋白表达均明显升高(P=0.003,P<0.001)。在免疫微环境方面,移植瘤组织中Teff细胞在大分割照射后略有增加,在常规分割放疗后与基线水平无明显差异;移植瘤组织中Treg细胞在大分割放疗前后无明显变化,在常规分割照射后明显增多。结论:常规分割放疗可诱导COX-2表达升高,并引起Treg细胞浸润增多,细胞毒性Teff浸润减少,导致免疫抑制;而大分割放疗不增加COX-2表达,也未导致Treg细胞增多。
Objective:To investigate changes of expression of cyclooxygenase 2(COX-2)before and after radiotherapy in esophageal squamous cell carcinoma(ESCC)and its effect on immune microenvironment.Methods:Peripheral venous blood samples of 56 ESCC patients who received radiotherapy were collected,and levels of COX-2,regulatory T cells(Treg)and cytotoxic effector T cells(Teff)in ESCC patients serum were detected before and after radiotherapy.ESCC were constructed in a rabbit model and applied radiotherapy of hypofractionated or conventional radiotherapy.Expression levels of COX-2 protein and its mRNA,infiltration of Treg and Teff cells in ESCC were detected.Results:Expression level of serum COX-2 in ESCC patients was gradually increased during and after radiotherapy(P=0.006,P<0.001).Proportions of CD3+CD8+Teff cells in peripheral blood of ESCC patients during and after radiotherapy were lower than the baseline level(P=0.070,P=0.003).Proportions of CD4+CD25+Treg cells in peripheral blood during and after radiotherapy were significantly higher than that before treatment(P=0.030,P<0.001).Results of animal experiments showed that mRNA and protein levels of COX-2 in transplanted tumor tissue of rabbit ESCC that received hypofractionated radiotherapy did not change significantly,while those increased significantly for the ones received conventional radiotherapy(P=0.003,P<0.001).In immune microenvironment,Teff cells increased slightly in transplanted tumor tissue of rabbit ESCC irradiated by hypofractionated,and no significant difference was observed in the conventional radiotherapy.Whereas Treg cells did not change significantly in hypo-fractionated radiotherapy tissues,there was a significant increase in conventional radiotherapy group.Conclusion:Conventional radio therapy can induce the increase of expression of COX-2,increase Treg cells infiltration and decrease Teff cells infiltration,lead to immu-nity inhibition,while hypofractionated radiotherapy did not increase expression of COX-2,nor did it lead to the increase of Treg cells.
作者
吴越
刘馨博
卢开进
戴春雷
孙光志
王鹏
沈小舟
李祎萍
韩高华
WU Yue;LIU Xinbo;LU Kaijin;DAI Chunlei;SUN Guangzhi;WANG Peng;SHEN Xiaozhou;LI Yiping;HAN Gaohua(Department of Infectious Disease,Taizhou People's Hospital,Taizhou 225300,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第7期1463-1468,共6页
Chinese Journal of Immunology
基金
江苏省卫生健康委面上项目(H2017076)
泰州市“311工程”项目(RCPY201813)。
关键词
食管鳞癌
环氧合酶2
放疗
免疫微环境
Esophageal squamous cell carcinoma
Cyclooxygenase 2
Radiotherapy
Immune microenvironment
