摘要
目的探讨抗程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)免疫疗法联合同步放化疗治疗局部晚期宫颈癌(LACC)的临床效果。方法回顾性选取2018年11月至2019年10月在秦皇岛市第一医院接受抗PD-1/PD-L1免疫疗法(帕博利珠单抗)联合同步放化疗[调强放疗(IMRT)+TP(紫杉醇+卡铂)化疗]治疗的LACC患者51例作为观察组,选取同期接受同步放化疗治疗的51例LACC患者作为对照组。比较两组客观缓解率、疾病控制率、肿瘤标志物[鳞状细胞癌抗原(SCCAg)、可溶性细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)、糖类抗原125(CA125)]、增殖凋亡指标[存活素(Survivin)、B淋巴细胞瘤-2基因(Bcl-2)、半胱氨酸蛋白酶-3(Caspase-3)、细胞凋亡促进物质(Bax)]、PD-1/PD-L1[可溶性PD-L1(sPD-L1)、CD4^(+)T细胞表面PD-1表达(PD-1 CD4^(+)T细胞)、CD8^(+)T细胞表面PD-1表达(PD-1 CD8^(+)T细胞)及CD14^(+)单核细胞表面PD-L1表达(PD-L1 CD14^(+)单核细胞)]、安全性及1年内生存率。结果(1)疾病控制及安全性:观察组客观缓解率、疾病控制率分别为80.39%(41/51)、92.16%(47/51),高于对照组的39.22%(20/51)、70.59%(36/51)(均P<0.05),但组间各毒副反应发生率差异均无统计学意义(均P>0.05);(2)肿瘤标志物及增殖凋亡指标:与治疗前比较,治疗后两组血清SCCAg、CYFRA21-1、CEA、CA125水平及Survivin、Bcl-2水平均显著降低,Caspase-3、Bax水平显著升高,且治疗后观察组以上指标均优于对照组(均P<0.05);(3)PD-1/PD-L1:治疗后,观察组sPD-L1、PD-1 CD4^(+)T细胞、PD-1 CD8^(+)T细胞、PD-L1 CD14^(+)单核细胞较治疗前显著降低(均P<0.05),且观察组sPD-L1、PD-1 CD4^(+)T细胞、PD-1 CD8^(+)T细胞、PD-L1 CD14^(+)单核细胞均低于对照组(均P<0.05);(4)生存情况:观察组1年内生存率高于对照组(P<0.05)。结论抗PD-1/PD-L1免疫疗法联合同步放化疗治疗LACC临床效果显著,可通过调控肿瘤标志物、增殖凋亡指标及PD-1/PD-L1表达来有效抑制病情进展,且不增加治疗风险,对提升患者生存率具有积极作用。
Objective To investigate the clinical effect of programmed death receptor-1(PD-1)/programmed death receptor ligand-1(PD-L1)immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer(LACC).Methods From November 2018 to October 2019,51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy(pembrolizumab)combined with concurrent radiotherapy and chemotherapy[intensity modulated radiotherapy(IMRT)+TP(taxol+carboplatin)chemotherapy]were selected as the observation group.51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group.The objective remission rate,disease control rate,tumor markers[squamous cell carcinoma antigen(SCCAg),soluble cytokeratin 19 fragment(CYFRA21-1),and carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125)],proliferation and apoptosis indicators[survivin(Survivin),B-cell lymphoma-2(Bcl-2),Caspase-3(Caspase-3),apoptosis-promoting substance(Bax)],PD-1/PD-L1[soluble PD-L1(sPD-L1),CD4^(+)T cell surface PD-1 expression(PD-1 CD4^(+)T cells),CD8^(+)T cell surface PD-1 expression(PD-1 CD8^(+)T cell)and CD14^(+)monocyte surface PD-L1 expression(PD-L1 CD14^(+)monocyte)],safety and survival rate within 1 year were compared between the two groups.Results(1)Disease control and safety:the objective response rate and disease control rate of the observation group were 80.39%(41/51)and 92.16%(47/51),respectively,which were higher than those of the control group by 39.22%(20/51)and 70.59%(36/51)(all P<0.05),but there was no significant difference in the incidence of side effects between the groups(all P>0.05).(2)Tumor markers and proliferation and apoptosis indexes:compared with those before treatment,the levels of serum SCCAg,CYFRA21-1,CEA,CA125,survivin and Bcl-2 in the two groups after treatment were significantly lower,and the levels of Caspase-3 and Bax were significantly higher;the above indexes in the observation group were better than those in the control group after treatment(all P<0.05).(3)PD-1/PD-L1:after treatment,sPD-L1,PD-1 CD4^(+)T cells,PD-1 CD8^(+)T cells and PD-L1 CD14^(+)monocytes in the observation group were significantly lower than those before treatment(all P<0.05).After treatment,the sPD-L1,PD-1 CD4^(+)T cells,PD-1 CD8^(+)T cells,PD-L1 CD14^(+)monocytes in the observation group were lower than those in the control group(all P<0.05).(4)Survival:the survival rate of the observation group was higher than that of the control group within 1 year(P<0.05).Conclusions The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant.It can effectively inhibit the progression of the disease by regulating tumor markers,proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment,and has a positive effect on improving the survival rate of patients.
作者
邵莎莎
曹丽艳
王光霞
付宝红
付占昭
Shao Shasha;Cao Liyan;Wang Guangxia;Fu Baohong;Fu Zhanzhao(Department of Oncology,the First Hospital of Qinhuangdao,Qinhuangdao 066000,China)
出处
《中国医师杂志》
CAS
2022年第6期916-921,共6页
Journal of Chinese Physician
关键词
宫颈肿瘤
化放疗
免疫疗法
程序性细胞死亡受体1
生物标记
肿瘤
Uterine cervical neoplasms
Chemoradiotherapy
Immunotherapy
Programmed cell death 1 receptor
Biomarkers,tumor