非霍奇金淋巴瘤PD-1抗体治疗患者免疫功能变化及不良反应预防研究  

Changes of immune function and prevention of adverse reactions in patients with non-Hodgkin's lymphoma treated with PD-1 antibody

作　　者：史玉 李天一[2] 王亚秋[1] 肖建波[1] SHI Yu;LI Tianyi;WANG Yaqiu;XIAO Jianbo(Third Department of Radiotherapy,Tangshan People's Hospital of Hebei Province,Tangshan 063000,China;Physical Examination Center,Tangshan People's Hospital,Tangshan 063000,China)

机构地区：[1]河北省唐山市人民医院放疗三科,唐山063000 [2]河北省唐山市人民医院体检中心,唐山063000

出　　处：《国际免疫学杂志》2024年第1期52-56,共5页International Journal of Immunology

基　　金：唐山市自然科学基金(20171293)。

摘　　要：目的探讨程序性细胞死亡受体-1(programmed cell death-1,PD-1)抗体对非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)患者免疫功能表达的影响,并分析不良反应的预防。方法选取2013年4月至2016年8月于河北省唐山市人民医院接受治疗的NHL确诊患者共计100例,并将其分为研究组和对照组,每组各50例。研究组接受PD-1抗体治疗,对照组患者依据病情给予NHL化疗治疗。免疫组化法检测治疗前后两组患者免疫检查点OX40、糖皮质激素诱导的肿瘤坏死因子受体(glucocorticoid-induced tumor necrosis factor receptor,GITR)、CD28、PD-1、血清T细胞免疫球蛋白黏液素3(T cell immnoglobulin and mucin 3,TIM-3)、淋巴细胞活化因子-3(lymphocyte activation gene-3,LAG-3)表达情况,并统计分析两组患者治疗后不良反应情况。结果治疗前,研究组与对照组患者共刺激性免疫检查点OX40、GITR、CD28表达水平,共抑制性免疫检查点PD-1、TIM-3、LAG-3表达水平及美国东部肿瘤合作组(Eastern Cooperative Group,ECOG)评分比较差异均无统计学意义(P>0.05)。治疗后,研究组患者OX40、GITR、CD28、TIM-3水平明显高于对照组,PD-1水平明显低于对照组,差异均有统计学意义[%:(9.75±3.02)比(6.35±2.85),(7.48±1.62)比(5.37±1.56),(16.37±3.42)比(13.46±3.56),(15.48±3.45)比(13.24±3.83),(0.87±0.22)比(1.32±0.36),t=5.79、6.63、4.17、3.07、7.54,P值均<0.05],两组患者LAG-3水平差异无统计学意义(P>0.05)。治疗后,研究组ECOG评分明显高于对照组,不良反应发生率明显低于对照组,差异有统计学意义[(4.61±1.46)分比(2.74±0.66)分,10.00%比26.00%,t=8.25、χ^(2)=4.34,P值均<0.05]。结论PD-1抗体治疗可有效提高NHL患者免疫共刺激分子的表达,同时抑制PD-1表达,下调患者免疫共抑制,以此改善NHL患者免疫系统状态。Objective To explore the effect of programmed cell death-1(PD-1)antibody on the immune function expression of patients with non-Hodgkin lymphoma(NHL),and to analyze the prevention of adverse reactions.Methods A total of 100 patients with NHL who received treatment at Tangshan People's Hospital in Hebei Province from April 2013 to August 2016 were selected,and divided into a study group and a control group,with 50 patients in each group.The research group received PD-1 antibody treatment,while the control group received NHL chemotherapy based on their condition.Immunohistochemical method was used to detect the expression of immune checkpoint OX40,glucocorticoid induced tumor necrosis factor receptor(GITR),CD28,PD-1,serum T cell immunoglobulin and mucin 3(TIM-3),and lymphocyte activation gene-3(LAG-3)in two groups of patients before and after treatment,and statistically analyze the adverse reactions.Result Before treatment,there were no statistically significant differences between the study group and the control group in the expression levels of OX40,GITR,CD28 at the co-stimulating immune checkpoint,and the expression levels of PD-1,TIM-3,and LAG-3 at the co-inhibitory immune checkpoint,as well as the Eastern Cooperative Group(ECOG)scores.After treatment,the levels of OX40,GITR,CD28,and TIM-3 in the study group were significantly higher than those in the control group,while the levels of PD-1 were significantly lower than those in the control group[%:(9.75±3.02)vs(6.35±2.85),(7.48±1.62)vs(5.37±1.56),(16.37±3.42)vs(13.46±3.56),(15.48±3.45)vs(13.24±3.83),(0.87±0.22)vs(1.32±0.36),t=5.79,6.63,4.17,3.07,7.54,all P values<0.05].There was no statistically significant difference in LAG-3 levels between the two groups of patients(P>0.05).After treatment,the ECOG score of the study group was significantly higher than that of the control group,and the incidence of adverse reactions was significantly lower than that of the control group[(4.61±1.46)points vs(2.74±0.66)points,10.00%vs 26.00%,t=8.25,χ^(2)=4.34,both

关 键 词：非霍奇金淋巴瘤 程序性细胞死亡受体-1抗体 抑制性免疫检查点 不良反应 

分 类 号：R733.1[医药卫生—肿瘤]