CTLA-4在肺腺癌细胞及其肿瘤浸润性淋巴细胞中表达的意义
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摘要
①目的 检测CTLA-4蛋白在肺腺癌细胞及其肿瘤浸润性淋巴细胞(TILs)中的表达,并探讨其与疾病进展的关系。②方法 选取肺腺癌患者57例(观察组),良性肺病变患者20例(对照组)。采用新鲜标本冰冻切片后行免疫组化检测CTLA-4蛋白表达。③结果 观察组肺腺癌细胞及其TILs中CTLA-4蛋白的阳性率均高于对照组(P<0.05);其中CTLA-4蛋白在肺腺癌细胞中的表达与分化程度有关,中-低分化组阳性率高于高分化组(P<0.05),而与性别、年龄、吸烟史、淋巴结转移及临床分期均无关(P>0.05)。CTLA-4蛋白在TILs中的表达与临床分期有关,Ⅲ-Ⅳ期组阳性率高于Ⅰ-Ⅱ组(P<0.05),而与性别、年龄、吸烟史、淋巴结转移及分化程度无关(P>0.05)。④结论 CTLA-4蛋白在肺腺癌细胞及其TILs中的过表达可能参与肺腺癌的疾病进展。
Objective To detect the CTLA-4 protein expression in lung adenocarcinoma and its tumor infiltrating lymphocytes(TILs),and to explore the relationship between the CTLA-4 protein expression and the progression of lung adenocarcinoma.Methods A total of 57 lung adenocarcinoma(the observation group) and 20 benign lung disease(the control group) were selected.The CTLA-4 protein expression was detected by immunohistochemistry after frozen sections of fresh specimens.Results The positive rate of the CTLA-4 protein in lung adenocarcinoma cells and its TILs in the observation group was higher than that in the control group(P<0.05).Among them,the expression of the CTLA-4 protein in lung adenocarcinoma cells was related to the degree of differentiation,and the positive rate in the middle-low differentiation group was higher than that in the high differentiation group(P<0.05),but was not related togender,age,smoking history,lymph node metastasis and the clinical stage(P>0.05).The CTLA-4 protein expression in TILs was related to clinical stages,the positive rate in Ⅲ-Ⅳphase was higher than in theⅠ-Ⅱ group(P<0.05),and had nothing to do with gender, age, smoking history, lymph node metastasis and the degree of differentiation(P>0.05).Conclusion It is suggested that over-expression of the CTLA-4 protein in lung adenocarcinoma and its TILs may be involved in the disease progression of lung adenocarcinoma.
Objective To detect the CTLA-4 protein expression in lung adenocarcinoma and its tumor infiltrating lymphocytes(TILs),and to explore the relationship between the CTLA-4 protein expression and the progression of lung adenocarcinoma.Methods A total of 57 lung adenocarcinoma(the observation group) and 20 benign lung disease(the control group) were selected.The CTLA-4 protein expression was detected by immunohistochemistry after frozen sections of fresh specimens.Results The positive rate of the CTLA-4 protein in lung adenocarcinoma cells and its TILs in the observation group was higher than that in the control group(P<0.05).Among them,the expression of the CTLA-4 protein in lung adenocarcinoma cells was related to the degree of differentiation,and the positive rate in the middle-low differentiation group was higher than that in the high differentiation group(P<0.05),but was not related togender,age,smoking history,lymph node metastasis and the clinical stage(P>0.05).The CTLA-4 protein expression in TILs was related to clinical stages,the positive rate in Ⅲ-Ⅳphase was higher than in theⅠ-Ⅱ group(P<0.05),and had nothing to do with gender, age, smoking history, lymph node metastasis and the degree of differentiation(P>0.05).Conclusion It is suggested that over-expression of the CTLA-4 protein in lung adenocarcinoma and its TILs may be involved in the disease progression of lung adenocarcinoma.
引文
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[2]王珊,董丽儒,任会强,等.肺腺癌中PD-1、PD-L1蛋白表达与K-RAS基因突变状态的相关性分析[J].临床与实验病理学杂志,2017,33(7):754-758
[3]Couzin-Frankel J.Breakthrough of the year2013cancer immunotherapy[J].Science,2013,342(6165):1432-1433
[4]Hellmann MD,Rizbi NA,Goldman JW,et al.Nivolumab plus ipilimumab as first-line treatment for advancednon-small-cell lung cancer(CheckMate 012):results of an open-label,phase 1,multicohort study[J].The Lancet Oncology,2017,18(1):31-41
[5]Zumerle S,Molon B,Viola A.Membrane rafts in T cell activation:a spotlight on CD28costimulation[J].FrontImmunol,2017,8:1467
[6]Capece D,Verzella D,Fischietti M,et al.Targeting costimulatory molecules to improve antitumor immunity[J].J Biomed Biotechnol,2012,2012:1-17
[7]Salama AK,Hodi FS.Cytotoxic T-lymphocyteassociated antigen-4[J].Clinical Cancer Research,2011,17(14):4622-4628
[8]Nirschl CJ,Drake CG.Molecular pathways:coexpression of immunecheckpoint molecules:signaling pathways and implications for cancerimmunotherapy[J].Clin Cancer Res,2013,19(18):4917-4924
[9]Shin D S,Ribas A.The evolution of checkpoint blockade as a cancertherapy:what's here,what's next?[J].Curr Opin Immunol,2015,33:23-35
[10]Antczak A,Pastuszak-Lewandoska D,Gorski P,et al.CTLA-4expression and polymorphisms in lung tissue of patients with diagnosed nonsmall-cell lung cancer[J].Biomed Res Int,2013:1-8
[11]郑海燕,李赟,王兴芬,等.gp96与免疫相关基因CTLA-4、CD8在肺癌组织芯片中的表达及意义[J].中国肺癌杂志,2010,13(8):790-794
[12]Bremnes RM,Busund LT,Kilvaer TL,et al.The role of tumor-infiltrating lymphocytes in development,progression and prognosis of nonsmall cell lung cancer[J].J Thorac Oncol,2016,11(6):789-800
[13]李艳双,杨丽娟.肿瘤微环境中淋巴细胞的种类与功能研究进展[J].河北联合大学学报(医学版),2016,18(3):245-249
[14]Fridman WH,Pages F,Sautes-Fridman C,et al.The immune contexture in human tumours:impact on clinicaloutcome[J].Nat Rev Cancer,2012,12(4):298-306
[15]Salgado R,Denkert C,Demaria S,et al.The evaluation of tumor-infiltrating lymphocytes(TILs)in breast cancer:recommendations by an international TILs working group 2014[J].Ann Oncol,2015,26(2):259-271
[16]Kalia V,Penny LA,Yuzefpolskiy Y,et al.Quiescence of memory CD8+T cells is mediated by regulatory T cells through inhibitory receptor CTLA-4[J].Immunity,2015,42(6):1116-1129
[17]Linterman MA,Denton AE.Treg cells and CT-LA-4:The ball and chain of the germinal center response[J].Immunity,2014,41(6):876-878
[18]Chen C,Chen D,Zhang Y,et al.Changes of CD4+CD25+FOXP3+and CD8+CD28-regulatory T cells in non-small cell lung cancer patients undergoing surgery[J].Int Immunopharmacol,2014,18(2):255-261
[19]郭洋.NSCLC患者T细胞表面CTLA-4、PD-1、TIM-3的表达水平和意义的研究[D].北京:北京市结核病胸部肿瘤研究所,2017
[20]韦腾飞,张军,吴豫,等.CD4+T细胞表面共抑制分子的表达水平与非小细胞肺癌疾病进展的关系[J].中华肿瘤杂志,2014,36(6):424-429