Fas-FasL在非小细胞肺癌中的表达情况及对免疫逃逸的调节分析
|
摘要
目的探讨Fas/FasL在非小细胞肺癌(NSCLC)中的表达及对免疫逃逸的作用。方法选取在我院治疗的NSCLC患者,酶联免疫吸附法检测入组患者血液Fas、Fasl含量,免疫组织化学法检测Fas、FasL在NSCLC组织、癌旁组织、正常肺组织的表达,TUNEL技术检测NSCLC细胞的凋亡情况。结果 Fas在肺癌组织中低表达,FasL在肺癌组织中高表达,FasL表达率与细胞组织学类型、分化程度、淋巴结转移相关,与TIL浸润程度呈负相关,Fas表达与肺癌细胞凋亡水平无关。结论 NSCLC组织中存在Fas低表达、FasL高表达,肺癌细胞发生免疫逃逸。
Objective To study the expression of Fas/FasL in non-small cell lung cancer(NSCLC), and analyze its function in regulation of immune escape. Methods Patients with NSCLC in our hospital were selected for analysis of the expression of Fas/FasL. The blood of patients with NSCLC was collected and performed with enzyme-linked immunosorbent to detect the content of Fas and Fasl. Immune histochemistry was conducted to analyze the expression of Fas and Fasl in NSCLC tissues, tissue adjacent to carcinoma, and normal lung tissue, TUNEL technology was performed to detect the apoptosis of NSCLC cell. Results The expression level of Fas was lower, but higher for FasL in lung cancer. The expression rate of FasL was related to the histological type, the degree of differentiation and lymph node metastasis, but negatively correlated with the degree of TIL infiltrating, however, with no significant correlation with the level of lung cancer cell apoptosis for Fas expression. Conclusion The lower expression of Fas and the overexpression of FasL in NSCLC tissues would lead to immune escape of lung cancer cells.
Objective To study the expression of Fas/FasL in non-small cell lung cancer(NSCLC), and analyze its function in regulation of immune escape. Methods Patients with NSCLC in our hospital were selected for analysis of the expression of Fas/FasL. The blood of patients with NSCLC was collected and performed with enzyme-linked immunosorbent to detect the content of Fas and Fasl. Immune histochemistry was conducted to analyze the expression of Fas and Fasl in NSCLC tissues, tissue adjacent to carcinoma, and normal lung tissue, TUNEL technology was performed to detect the apoptosis of NSCLC cell. Results The expression level of Fas was lower, but higher for FasL in lung cancer. The expression rate of FasL was related to the histological type, the degree of differentiation and lymph node metastasis, but negatively correlated with the degree of TIL infiltrating, however, with no significant correlation with the level of lung cancer cell apoptosis for Fas expression. Conclusion The lower expression of Fas and the overexpression of FasL in NSCLC tissues would lead to immune escape of lung cancer cells.
引文
[1]Brown MA.Genetics of ankylosing spondylitis[J].Curr Opin Rheumatol,2010,22(2):126-132.
[2]Punsawad C,Viryavejakul P,Settharamote C.Enhanced expression of Fas and Fas L modulates apoptosis in the lungs of severe Pfalciparum malaria patients with pulmonary edema[J].Int J Clin Pathol,2015,8(9):10002-10013.
[3]Wu GZ.Clinicopathological significance of Fas and Fas ligand expressions in esophageal cancer[J].Am J Cancer Res,2015,5(9):2865-2871.
[4]Yao YW,Zhang GH,Zhang YY,et al.Lipo poly saccharide pretreatment protects against ischemia/reperfusion Injury via increase of HSP70 and inhibition of nf-kappa B[J].Cell Stress Chaperon,2011,1(3):287-296.
[5]Baban B,Liu JY,Mozaffari MS.Pressure overload regulates expression of cytokines,gamma H2AX,and growtharrest-and dna damage inducible protein 153 via glycogen synthase kinase-3 beta in ischemic-reperfused hearts[J].Hypertension,2013,21(1):95-....104.
[6]Calmon-Hamaty F.Targeting the Fas/Fas L system in rheumatoid arthritis therapy:promising or risky[J].Cytokine,2015,75(2):228-233.
[7]Tsalkidou EG,Tsaroucha AK,Chatzaki E.The effects of apigenin on the expression of Fas/Fas L apoptotic pathway in warm liver ischemia-reperfusion injury in rats[J].Biomed Res Int,2014,6(2014):157216.
[9]Asensio C,Zapata A,García-Ahijado J,et al.Fas expression is associated with a better prognosis in laryngeal squamous cell carcinoma[J].Anticancer Res,2007,27(6B):4083-4086.
[9]Han W.Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population[J].Plos One,2013,8(8):e71656.
[10]Wu X,Xu T,Li D,et al.ERK/PP1a/PLB/SERCA2a and JNK pathways are involved in luteolin mediated protection of rat hearts and cardio myocytes following Ischemia/Reperfusion[J].PLo S One,2013,8(12):1-12.
[11]Ahebe M,Doherty TM,Wassie L,et al.Expression of apoptosisrelated genes in an Ethiopian cohort study correlates with tuberculosis clinical status[J].Eur J Immunol,2010,40(1):291-301.
[12]Li ML,Shu XH,Shu XH,et al.Antitumor effects of recombinant human interleukin-6 on mouse bladder carcinoma through Fasmediated apoptosis[J].Cancer Chemother Pharmacol,2010,66(5):981-986.
[13]Chinda K,Sanit J,Chattipakorn S,et al.Dipeptidyl peptidase 4inhibitor reduces infarct size and preserves cardiac function via mitochondrial protection inischaemia-reperfusion rat heart[J].Diab Vasc Dis Res,2014,11(2):75-83.
[14]宿杰,田大力,陈东义,等.Fas/Fas L在小细胞肺癌和转移淋巴结中的表达及临床意义[J].中国医科大学学报,2006,35(3):282-283.
[15]刘晓红,王心明,王延龄.Fas/Fas L在乳腺疾病发生发展过程中作用的研究[J].中华实验诊断学,2007,11(2):158-162.
[16]Miller MR,Mandell JB,Beatty KM.Splenectomy promotes indirect elimination of intraocular tumors by CD8+T cells that is associated with IFNγ-and Fas/Fas L dependent activation of intratumoral macrophages[J].Cancer Immunol Res,2014,2(12):1175-1185.
[17]Bork PM,Schmitz ML,Kuhnt M,et al.Sesquiter penelactone containing Mexican Indian medicinal plants and puresesquit erpenelact ones as potent inhibitors of transcription factor NFNb[J].FEBS Lett,1997,402(1):85-90.
[18]王强,杨志雄,廖思海.Fas/Fas L和Caspase-3在肺癌中的表达及其临床意义[J].现代肿瘤医学,2009,2(17):248-251.
[19]刘颖,吴金如,高元勋.Fas/Fas L在非小细胞肺癌中的表达及其与肿瘤免疫和细胞凋亡的关系[J].西安交通大学学报(医学版),2011,1(32):6-9..
[2]Punsawad C,Viryavejakul P,Settharamote C.Enhanced expression of Fas and Fas L modulates apoptosis in the lungs of severe Pfalciparum malaria patients with pulmonary edema[J].Int J Clin Pathol,2015,8(9):10002-10013.
[3]Wu GZ.Clinicopathological significance of Fas and Fas ligand expressions in esophageal cancer[J].Am J Cancer Res,2015,5(9):2865-2871.
[4]Yao YW,Zhang GH,Zhang YY,et al.Lipo poly saccharide pretreatment protects against ischemia/reperfusion Injury via increase of HSP70 and inhibition of nf-kappa B[J].Cell Stress Chaperon,2011,1(3):287-296.
[5]Baban B,Liu JY,Mozaffari MS.Pressure overload regulates expression of cytokines,gamma H2AX,and growtharrest-and dna damage inducible protein 153 via glycogen synthase kinase-3 beta in ischemic-reperfused hearts[J].Hypertension,2013,21(1):95-....104.
[6]Calmon-Hamaty F.Targeting the Fas/Fas L system in rheumatoid arthritis therapy:promising or risky[J].Cytokine,2015,75(2):228-233.
[7]Tsalkidou EG,Tsaroucha AK,Chatzaki E.The effects of apigenin on the expression of Fas/Fas L apoptotic pathway in warm liver ischemia-reperfusion injury in rats[J].Biomed Res Int,2014,6(2014):157216.
[9]Asensio C,Zapata A,García-Ahijado J,et al.Fas expression is associated with a better prognosis in laryngeal squamous cell carcinoma[J].Anticancer Res,2007,27(6B):4083-4086.
[9]Han W.Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population[J].Plos One,2013,8(8):e71656.
[10]Wu X,Xu T,Li D,et al.ERK/PP1a/PLB/SERCA2a and JNK pathways are involved in luteolin mediated protection of rat hearts and cardio myocytes following Ischemia/Reperfusion[J].PLo S One,2013,8(12):1-12.
[11]Ahebe M,Doherty TM,Wassie L,et al.Expression of apoptosisrelated genes in an Ethiopian cohort study correlates with tuberculosis clinical status[J].Eur J Immunol,2010,40(1):291-301.
[12]Li ML,Shu XH,Shu XH,et al.Antitumor effects of recombinant human interleukin-6 on mouse bladder carcinoma through Fasmediated apoptosis[J].Cancer Chemother Pharmacol,2010,66(5):981-986.
[13]Chinda K,Sanit J,Chattipakorn S,et al.Dipeptidyl peptidase 4inhibitor reduces infarct size and preserves cardiac function via mitochondrial protection inischaemia-reperfusion rat heart[J].Diab Vasc Dis Res,2014,11(2):75-83.
[14]宿杰,田大力,陈东义,等.Fas/Fas L在小细胞肺癌和转移淋巴结中的表达及临床意义[J].中国医科大学学报,2006,35(3):282-283.
[15]刘晓红,王心明,王延龄.Fas/Fas L在乳腺疾病发生发展过程中作用的研究[J].中华实验诊断学,2007,11(2):158-162.
[16]Miller MR,Mandell JB,Beatty KM.Splenectomy promotes indirect elimination of intraocular tumors by CD8+T cells that is associated with IFNγ-and Fas/Fas L dependent activation of intratumoral macrophages[J].Cancer Immunol Res,2014,2(12):1175-1185.
[17]Bork PM,Schmitz ML,Kuhnt M,et al.Sesquiter penelactone containing Mexican Indian medicinal plants and puresesquit erpenelact ones as potent inhibitors of transcription factor NFNb[J].FEBS Lett,1997,402(1):85-90.
[18]王强,杨志雄,廖思海.Fas/Fas L和Caspase-3在肺癌中的表达及其临床意义[J].现代肿瘤医学,2009,2(17):248-251.
[19]刘颖,吴金如,高元勋.Fas/Fas L在非小细胞肺癌中的表达及其与肿瘤免疫和细胞凋亡的关系[J].西安交通大学学报(医学版),2011,1(32):6-9..