摘要
目的比较HPV16感染的中晚期宫颈鳞患者外周血和癌组织中CD4+、CD8+T细胞上CTLA-4表达水平的差异及临床特征的相关性,分析患者外周血中CTLA-4表达水平在放射治疗过程中的变化,为中晚期宫颈鳞癌患者放疗联合免疫治疗的探索提供理论基础。方法收集2017年2月-2018年8月,就诊于新疆医科大学附属肿瘤医院-妇科放射治疗科的63例HPV16型感染的中晚期宫颈鳞癌患者。收集患者放射治疗前、中及治疗结束时外周肘静脉血,患者行治疗前的宫颈癌组织,分离外周血中PBMCs和组织中的TILs。采用多色流式细胞技术(FCM)检测PBMCs和TILs中T细胞上CTLA-4的表达。结果(1)HPV16感染的中晚期宫颈癌鳞患者PBMCs中CD8+T细胞上CTLA-4的表达22.50(8.36,25.40)%高于TILs中4.95(2.60,15.80)%,差异有统计学意义(P<0.001);(2)患者PBMCs中CD4+CTLA-4+T细胞在病理分级中比较,由低到高分别为低分化组4.33(2.37,7.25)%,中分化组4.97(1.48,8.78)%和乳头状组17.55(8.29,31.90)%,差异有统计学意义(P<0.05);患者PBMCs中CD8+CTLA-4+T细胞在病理分级中表达逐渐升高,低分化组21.80(11.69,26.75)%、中分化组22.20(7.21,29.33)%和乳头状组43.25(31.30,49.38)%,差异有统计学意义(P<0.05);(3)患者PBMCs中CD4+T细胞上CTLA-4表达量随放疗进度呈升高趋势,放疗前3.94(1.85,5.70)%、放疗中6.80(3.38,41.13)%、放疗结束时7.86(4.47,13.23)%,差异均有统计学意义(P<0.05)。结论HPV16感染的中晚期宫颈鳞癌患者外周血和癌组织T细胞中均可检测到CTLA-4分子的表达,放射治疗过程中T细胞上CTLA-4的表达呈动态变化。
Objective Compare the CTLA-4 expression onCD4+or CD8+T cells in the peripheral blood and tumour tissue among the patients with locally advanced cervical squamous cancer(CSCC)and HPV16 infection before and during the treatment course.To investigate the correlation of CTLA-4 expression with clinical features so as to provide evidence for the integration of anti-CTLA-4 immunotherapy to the chemotherapy and/or radiotherapy for locally advanced cervical cancer patients.Methods From February 2017 to August 2018,63 patients with advanced CSCC and HPV16 infection admitted to the Affiliated Cancer Hospital of Xinjiang Medical University were recruited into this study.Peripheral venous blood from each patient were collected before,during and at the end of treatment.Meanwhile,cervical cancer tissues were collected before treatment.Peripheral blood mononuclear cell(PBMCs)and tumour infiltrated lymphocytes(TILs)were isolated from blood and tissue,respectively.The expression of CTLA-4 on CD4+and CD8+T cells in the PBMCs and TILs was measured by multicolor flow cytometry.Correlation of CTLA-4 expression and clinical characteristics were analyzed.Results(1)In the patientswith advanced cervicalcancer infected by HPV16,the CTLA-4 expression on CD8+T cells was 22.50(8.36,25.40)%in the PBMCs,higher than that in the TILs:4.95(2.60,15.80)%(P<0.001).(2)The expressions of CTLA-4+on CD4+T cells in the PBMCs werecorrelated to pathological grades:4.33(2.37,7.25)%,4.97(1.48,8.78)%and 17.55(8.29,31.90)%in low,mid,and high differentiation groups respectively(P<0.05).And the expressions of CTLA-4+CD8+T cells in the PBMCs were alsocorrelated to the pathological grades:21.80(11.69,26.75)%,22.20(7.21,29.33)%and 43.25(31.30,49.38)%inlow,midand high differentiation groups respectively,with statistically significant differences(P<0.05).(3)The expressions of CTLA-4+cells in CD4+T cells in the PBMCs was increased gradually during the course of rediotherapy treatment:3.94(1.85,5.70)%before the treatment and 6.80(3.38,41.13)%during the treatment compared,and 7.86(4.47,13.23)%at the end of the treatment respectively,and the differences were statistically significant P<0.05).Conclusion CTLA-4 expression can be detected on T cells in the peripheral bloodand tumour tissue of patients with cervical squamous cell carcinoma,its expressionon T cells was dynamically changed during the course of radiotherapy.
作者
范佩文
马苗苗
冯亚宁
王若峥
FAN Peiwen;MA Miaomiao;FENG Yaning;WANG Ruozheng(Institute for Cancer Research of Xinjiang Uyghur Autonomous Region, Urumqi 830011, China;Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi 830011, China;Key Laboratory of Cancer Immunotherapy and Radiotherapy, Chinese Academy of Medical Sciences, Urumqi, 830011, China;Second Department of Radiation Oncology, People′s Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830011, China)
出处
《新疆医科大学学报》
CAS
2020年第9期1129-1135,共7页
Journal of Xinjiang Medical University
基金
国家自然科学基金(U1603282)
中国医学科学院院外重点实验室建设项目(2018PT31050)。
关键词
宫颈鳞癌
人乳头瘤病毒
CTLA-4
临床特征
cervical squamous cell carcinoma(CSCC)
humanpapillomavirus(HPV)
CTLA-4
clinical features
