Please wait a minute...
浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (5): 523-528    DOI: 10.3785/j.issn.1008-9292.2017.10.12
原著     
记忆T细胞在行放射治疗的非小细胞肺癌患者中的表达及其预后预测价值
胡静1, 郑璐1, 张欢乐1, 张三典1, 徐国栋2
1. 浙江省宁波市医疗中心李惠利医院放疗科, 浙江 宁波 315040;
2. 浙江省宁波市医疗中心李惠利医院心胸外科, 浙江 宁波 315040
Expression and prognostic value of memory T lymphocyte in patients with non-small cell lung cancer following radiotherapy
HU Jing1, ZHENG Lu1, ZHANG Huanle1, ZHANG Sandian1, XU Guodong2
1. Department of Radiotherapy, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, Zhejiang Province, China;
2. Department of Cardiothoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, Zhejiang Province, China
 全文: PDF(972 KB)  
摘要：

目的：分析记忆T细胞在行放射治疗的非小细胞肺癌（NSCLC）患者中的表达及其对预后的预测价值。方法：收集2010年2月至2012年5月浙江省宁波市医疗中心李惠利医院共46例接受放射治疗的NSCLC患者和50名健康体检者。应用流式细胞术检测外周血CD4+、CD8+的中央型记忆T细胞（TCM）和效应型记忆T细胞（TEM）的表达。采用多因素Cox回归模型分析患者临床特征及记忆T细胞变化与总生存时间的相关性，并采用Kaplan-Meier法绘制生存曲线。结果：NSCLC患者放射治疗前外周血CD4+TCM、CD4+TEM、CD8+TCM和CD4+/CD8+TEM比值较健康对照组低，CD4+/CD8+TCM比值较健康对照组高（均P<0.05）；放射治疗4周时，NSCLC患者外周血CD4+TCM、CD4+TEM、CD8+TCM和CD4+/CD8+TEM比值较放射治疗前明显降低（均P<0.05），而CD8+TEM和CD4+/CD8+TCM比值较放射治疗前升高（均P<0.05）；放射治疗12周时，NSCLC患者外周血CD4+TCM、CD4+TEM和CD8+TCM较放射治疗4周时升高（均P<0.05）。多因素Cox回归分析结果显示，放射治疗后CD4+TCM的变化趋势与NSCLC患者的总生存时间有相关性（95% CI：1.135~2.994，P<0.01）。放射治疗后CD4+TCM呈下降趋势者的存活率为23.1%，总生存时间为10.7个月（95% CI：0.29~12.41）；CD4+TCM保持稳定者的存活率为52.7%，总生存时间为27.4个月（95% CI：0.00~31.26）；CD4+TCM上升者的存活率为66.4%，总生存时间为37.4个月（95% CI：0.33~29.21）。结论：NSCLC患者放射治疗后初期表现出明显的免疫抑制，之后有逐渐改善的趋势。放射治疗后记忆T细胞的变化趋势对患者的预后有一定的预测价值。
关键词： 非小细胞肺/放射疗法;  抗原;  CD4/免疫学;  抗原;  T淋巴细胞/免疫学;  预后;  CD8/免疫学;  癌    
Abstract:

Objective: To investigate the expression and prognostic value of memory T lymphocyte in patients with non-small cell lung cancer(NSCLC) following radiotherapy.Methods: Forty-six patients with NSCLC receiving radiotherapy in Ningbo Medical Center Lihuili Hospital from February 2010 to May 2012 were enrolled in the study and 50 healthy subjects served as the control group. The central memory T cell (TCM) and effector memory T cell (TEM) in peripheral blood CD4+, CD8+ cells were detected by flow cytometry. Survival of patients was analyzed by Kaplan-Meier curve, and the relationship between clinical features, memory T lymphocyte changes and overall survival was analyzed by multivariate Cox regression model.Results: CD4+TCM, CD4+TEM, CD8+TCM levels and CD4+/CD8+ TEM of NSCLC patients were significantly lower than those of the control group, while CD4+/CD8+ TCM was significantly higher than that of the control group(all P<0.05). In NSCLC patients, CD4+TCM, CD4+TEM and CD8+TCM were decreased and CD8+TEM levels were increased 4 weeks after radiotherapy(all P<0.05); CD4+TCM, CD4+TEM and CD8+TCM at 12-week after radiotherapy were increased significantly compared with those at 4-week after radiotherapy(all P<0.05). Multivariate Cox regression analysis showed that the change of CD4+TCM after radiotherapy was correlated with the overall survival (95% CI:1.135-2.994, P<0.01). The survival rate and overall survival time for patients with decreasing CD4+ TCM were 23.1% and 10.7 months (95% CI:0.29-12.41), while those of patients with stable CD4+ TCM were 52.7% and 27.4 months (95% CI:0.00-31.26), and those of patients with increasing CD4+ TCM were 66.4% and 37.4 months (95% CI:0.33-29.21), respectively. Conclusions: NSCLC patients show a significant immunosuppression at the initial stage after radiotherapy, and then a gradual improvement. Change of memory T lymphocyte after radiotherapy can be used to help predicting the prognosis of the patients.
Key words: Carcinoma,non-small-cell lung/radiotherapy    T-lymphocytes/immunology    Antigens,CD8/immunology    Prognosis    Antigens,CD4/immunology
收稿日期: 2017-06-29 出版日期: 2017-10-25
CLC:  R734.2  
基金资助:

浙江省自然科学基金（LQ16H160002）
作者简介: 胡静(1985-),女,硕士研究生,主治医师,主要从事肺癌、食管癌等肿瘤的临床和基础研究;E-mail:jinglehu@163.com;http://orcid.org/0000-0002-4129-3394
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　

引用本文:

胡静 等. 记忆T细胞在行放射治疗的非小细胞肺癌患者中的表达及其预后预测价值[J]. 浙江大学学报（医学版）, 2017, 46(5): 523-528.

HU Jing, ZHENG Lu, ZHANG Huanle, ZHANG Sandian, XU Guodong. Expression and prognostic value of memory T lymphocyte in patients with non-small cell lung cancer following radiotherapy. Journal of ZheJiang University(Medical Science), 2017, 46(5): 523-528.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2017.10.12    或    http://www.zjujournals.com/xueshu/med/CN/Y2017/V46/I5/523

[1] 何晓烨,蔡映云.CD4+ CD25+调节性T细胞及Foxp3基因在不同淋巴结转移状态的非小细胞肺癌患者中的表达差异[J].中国免疫学杂志,2012,28(1):33-37. HE Xiaoye, CAI Yingyun. The difference of CD4+ CD25+ regulatory T cells and Foxp3 expression in non-small cell lung cancer patients with different lymph node meatastasis status[J]. Chinese Jorunal of Immunology,2012,28(1):33-37. (in Chinese)
[2] 何以丰,狄文.癌相关CD8+记忆T细胞在过继免疫治疗中的应用[J].中国肿瘤生物治疗杂志,2012,19(2):116-121. HE Yifeng, DI Wen. Cancer-associated CD8+ memory T cells in the application of adoptive immunotherapy[J]. Chinese Journal of Cancer Biotherapy,2012,19(2):116-121. (in Chinese)
[3] 王心静,曹志红,张金花,等.活动性肺结核病人外周血CD4+/CD8+Tim-3+T细胞群内记忆细胞分布特点[J].免疫学杂志,2012,7(4):604-606. WANG Xinjing, CAO Zhihong, ZHANG Jinhua, et al. Distribution of memory T cells in CD4+/CD8+Tim-3+/Tim-3- T cell population in PBMCs from patients with active pulmonary tuberculosis[J]. Immunological Journal,2012,7(4):604-606. (in Chinese)
[4] SATHALIYAWALA T, KUBOTA M, YUDANIN N, et al. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets[J]. Immunity,2013,38(1):187-197.
[5] MASOPUST D, SCHENKEL J M. The integration of T cell migration, differentiation and function[J]. Nat Rev Immunol,2013,13(5):309-320.
[6] FARBER D L, YUDANIN N A, RESTIFO N P. Human memory T cells:generation, compartmentalization and homeostasis[J]. Nat Rev Immunol,2014,14(1):24-35.
[7] PRADO-GARCIA H, ROMERO-GARCIA S, AGUILAR-CAZARES D, et al. Tumor-induced CD8+ T-cell dysfunction in lung cancer patients[J]. Clin Dev Immunol,2012,2012:741741.
[8] 鄢仁晴,方宁,赵建军,等.肺结核患者外周血CD4+和CD8+记忆性T细胞亚群、IL-17、IL-27表达的初步探讨[J].中国免疫学杂志,2012,28(10):930-935. YAN Renqing, FANG Ning, ZHAO Jianjun, et al. Preliminary study on the expression of CD4+ and CD8+ memory T cells subgroups and the levels of IL-17/IL-27 from patients' peripheral blood with pulmonary tuberculosis[J]. Chinese Journal of Immunology,2012,28(10):930-935. (in Chinese)
[9] 徐永茂,徐冬云,张南征,等.NP方案化疗同步放疗并序贯过继免疫细胞治疗非小细胞肺癌的临床研究[J].中华肿瘤防治杂志,2011,18(13):1032-1035. XU Yongmao, XU Dongyun, ZHANG Nanzheng, et al. Effection of NP concurrent chemotherapy radiotherapy and sequential adoptive immunity cell for locally advanced non-small cell lung cancer[J]. Chinese Journal of Cancer Prevention and Treatment,2011,18(13):1032-1035. (in Chinese)
[10] BARRY M, BLEACKLEY R C. Cytotoxic T lymphocytes:all roads lead to death[J]. Nat Rev Immunol,2002,2(6):401-409.
[11] SHENG S Y, GU Y, LU C G, et al. The distribution and function of human memory T cell subsets in lung cancer[J]. Immunologic Research,2017,65(3):639-650.
[12] 陈卓,于卫江.注射用黄芪多糖对非小细胞肺癌放疗的作用及对机体免疫的影响[J].中国实验方剂学杂志,2013,19(6):309-313. CHEN Zhuo, YU Weijiang. Effect of astragalus ploysaccharide injection in radiotherapy on non-small cell lung cancer and human immune function[J]. Chinese Journal of Experimental Traditional Medical Formulae,2013,19(6):309-313. (in Chinese)
[13] MOLINA J R, YANG P, CASSIVI S D, et al. Non-small cell lung cancer:epidemiology, risk factors, treatment, and survivorship[J]. Mayo Clin Proc,2008,83(5):584-594.
[14] 石远凯,牛奕.美国国家综合癌症网非小细胞肺癌治疗指南2007年第一版介绍[J].中华肿瘤杂志,2007,29(10):799-800. SHI Yuankai, NIU Yi. NCCN guidelines for treatment of non-small cell lung cancer (2007 version 1)[J]. Chinese Journal of Oncology,2007,29(10):799-800. (in Chinese)
[15] CHEN I H, LAI Y L, WU C L, et al. Immune impairment in patients with terminal cancers:influence of cancer treatments and cytomegalovirus infection[J]. Cancer Immunol Immunother,2010,59(2):323-334.
[16] DEVITA V T, ROSENBERG S A. Two hundred years of cancer research[J]. N Engl J Med,2012,366(23):2207-2214.
[17] 李艳,郭其森.晚期非小细胞肺癌维持治疗进展[J].中华肿瘤防治杂志,2014,21(10):800-804. LI Yan, GUO Qisen. Research progress of maintanence therapy in advanced non-small cell lung cancer[J]. Chinese Journal of Cancer Prevention and Treatment,2014,21(10):800-804. (in Chinese)
[1] 潘静颖 等. PET-CT与乳腺癌分子病理分型、治疗反应及预后的相关性研究进展[J]. 浙江大学学报（医学版）, 2017, 46(5): 473-480.
[2] 潘瑶 等. 胰腺癌的影像学精准诊断与评估[J]. 浙江大学学报（医学版）, 2017, 46(5): 462-467.
[3] 李爱静 等. 动态增强磁共振成像参照物模型定量参数与乳腺癌预后因素及分子病理分型的关系[J]. 浙江大学学报（医学版）, 2017, 46(5): 505-510.
[4] 邝平定 等. 双能量CT对非小细胞肺癌淋巴结转移的诊断价值[J]. 浙江大学学报（医学版）, 2017, 46(5): 511-516.
[5] 张美霞 等. 静脉溶栓获益的最大梗死体积阈值与急性缺血性卒中患者发病时间的关系[J]. 浙江大学学报（医学版）, 2017, 46(4): 384-389.
[6] 赖针珍 等. 动态CT血管造影评估急性基底动脉闭塞患者侧支血流与再灌注治疗预后的关系[J]. 浙江大学学报（医学版）, 2017, 46(4): 371-376.
[7] 冯学问 等. 急性缺血性卒中患者血管内治疗后应用替罗非班的安全性及预后分析[J]. 浙江大学学报（医学版）, 2017, 46(4): 397-404.
[8] 田华 等. CD97免疫表位对乳腺癌细胞株MDA-MB231生物学行为的影响[J]. 浙江大学学报（医学版）, 2017, 46(4): 341-348.
[9] 王庆松 等. 基于CT灌注成像的侧支评分预测急性前循环大血管闭塞患者动脉取栓治疗预后的价值[J]. 浙江大学学报（医学版）, 2017, 46(4): 377-383.
[10] 张晓群 等. 不同药物洗脱支架对冠状动脉小血管病变患者预后影响的meta分析[J]. 浙江大学学报（医学版）, 2017, 46(3): 305-314.
[11] 姚国荣,傅云峰,李艳丽,周彩云,吕卫国. 卵巢上皮性癌组织中DNAJB11的表达及临床意义[J]. 浙江大学学报（医学版）, 2017, 46(2): 173-178.
[12] 姚国荣 等. 卵巢上皮性癌组织中DNAJB11的表达及临床意义[J]. 浙江大学学报（医学版）, 2017, 46(2): 173-178.
[13] 蔡成,王建平,钟志凤,戴志慧,王庆华,董武真,施红旗,刘庆伟,杜金林. 缺氧诱导因子1α和CD133预测直肠癌患者新辅助放化疗疗效的临床研究[J]. 浙江大学学报（医学版）, 2017, 46(1): 36-43.
[14] 陈刚,张鼎,应亚草,王志峰,陶伟,朱皓,张景峰,彭志毅. 国产载药微球经动脉化疗栓塞治疗不可切除原发性肝癌的临床研究[J]. 浙江大学学报（医学版）, 2017, 46(1): 44-51.
[15] 刘军 等. 机体炎症因子和氧化应激标志物介导姜黄素抑制骨性关节炎的作用机制[J]. 浙江大学学报（医学版）, 2016, 45(5): 461-468.