非小细胞肺癌患者外周血Treg和Th17水平及意义
|
摘要
[目的]探讨非小细胞肺癌(NSCLC)患者外周血中Treg和Th17细胞的变化及其意义。[方法]收集40例NSCLC患者和20名健康对照的外周血样本,采用流式细胞术检测外周血中Treg和Th17细胞占CD4+T细胞的比例,酶联免疫吸附实验法检测TGF-β和IL-17水平。[结果]肺癌患者外周血中Treg细胞和Th17细胞比例均显著性高于健康对照组(分别为6.65%±3.70%vs 4.06%±1.23%和1.20%±1.19%vs 0.44%±0.13%,P<0.05)。外周血Treg和Th17细胞表达与NSCLC患者分期等无相关性(P>0.05)。肺癌患者外周血TGF-β和IL-17水平明显高于对照组(分别为25.05±3.19 vs 15.96±3.65和4.36±2.79 vs 2.01±1.83,P<0.05)。[结论]NSCLC患者外周血中Treg和Th17细胞以及相关细胞因子均高表达,Treg细胞以及Th17细胞参与了肺癌的发生和发展。
[Objective] To determine the levels of Treg and Th17 cells in peripheral blood of patients with non-small cell lung cancer(NSCLC) and their significance. [Methods] The peripheral blood samples of 40 NSCLC patients and 20 health subjects were collected. The Treg and Th17 cells in peripheral blood were detected by flow cytometry,the serum TGF-β and IL-17 levels were measured by ELISA.The relationship between the expression of Treg and Th17 cells and clinicopathological features of NSCLC patients was analyzed.[Results] The expression of Treg and Th17 cells in peripheral blood of NSCLC patients were significantly higher than that in healthy controls(6.65%±3.70% vs 4.06%±1.23% and 1.20%±1.19% vs 0.44%±0.13%,both P<0.05).However the levels of Treg and Th17 were not correlated with the stage of NSCLC(P>0.05).The serum TGF-βand IL-17 levels in NSCLC patients were significantly higher than those in controls(25.05±3.19 vs15.96±3.65 and 4.36±2.79 vs 2.01±1.83,both P<0.05). [Conclusion] Treg and Th17 cells and their associated cytokines TGF-β and IL-17 are highly expressed in peripheral blood of NSCLC patients.
[Objective] To determine the levels of Treg and Th17 cells in peripheral blood of patients with non-small cell lung cancer(NSCLC) and their significance. [Methods] The peripheral blood samples of 40 NSCLC patients and 20 health subjects were collected. The Treg and Th17 cells in peripheral blood were detected by flow cytometry,the serum TGF-β and IL-17 levels were measured by ELISA.The relationship between the expression of Treg and Th17 cells and clinicopathological features of NSCLC patients was analyzed.[Results] The expression of Treg and Th17 cells in peripheral blood of NSCLC patients were significantly higher than that in healthy controls(6.65%±3.70% vs 4.06%±1.23% and 1.20%±1.19% vs 0.44%±0.13%,both P<0.05).However the levels of Treg and Th17 were not correlated with the stage of NSCLC(P>0.05).The serum TGF-βand IL-17 levels in NSCLC patients were significantly higher than those in controls(25.05±3.19 vs15.96±3.65 and 4.36±2.79 vs 2.01±1.83,both P<0.05). [Conclusion] Treg and Th17 cells and their associated cytokines TGF-β and IL-17 are highly expressed in peripheral blood of NSCLC patients.
引文
[1]Sakaguchi S,Yamaguchi T,Nomura T,et al.Regulatory T cells and immune tolerance[J].Cell,2008,133(5):775-787.
[2]Noack M,Miossec P.Th17 and regulatory T cell balance in autoimmune and inflammatory diseases[J].Autoimmun Rev,2014,13(6):668-677.
[3]Whiteside TL.Regulatory T cell subsets in human cancer:are they regulating for or against tumor progression?[J].Cancer Immunol Immunother,2014,63(1):67-72.
[4]Fang Q,Dai AG,Jiang YL.Research progress of Th17/Treg and pulmonary diseases[J].Journal of Clinical Pulmonary Medicine,2016,21(5):899-902.[万琴,戴爱国,蒋永亮.Th17/Treg与肺部疾病的研究进展[J].临床肺科杂志,2016,21(5):899-902.]
[5]Zou Q,Yao X,Feng J,et al.Praziquantel facilitates ifngamma-producing CD8 T cells and IL-17-producing CD8T cells responses to DNA vaccination in mice[J].PLo S One,2011,6(10):e25525.
[6]Sun WH,Wei XF,Zhao P,et al.Changes in Treg cells and their cytokine production in the peripheral blood of gastric cancer patients following immunotherapy with DCCIK cells[J].Chin J Cancer Biother,2015,22(1):79-83.[孙伟红,魏晓芳,赵鹏,等.胃癌患者DC-CIK治疗前后外周血Treg细胞及相关细胞因子的变化[J].中国肿瘤生物治疗杂志,2015,22(1):79-83.]
[7]Zhen QH,Wang N,Song TJ,et al.Change of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances[J].Journal of Jilin University(Med Edition),2016,42(4):659-664.[郑全辉,王娜,宋天姣,等.肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义[J].吉林大学学报(医学版),2016,42(4):659-664.]
[8]Wang HB,Guo CL,Cheng W,et al.Analysis of Treg cells in hepatocellular carcinoma and their clinical significance[J].Journal of Chinese Oncology,2015,21(2):133-137.[王宏波,郭存丽,程文,等.肝细胞癌患者病灶局部Treg细胞分析及其临床意义[J].肿瘤学杂志,2015,21(2):133-137.]
[9]Liu F,Lang R,Zhao J,et al.CD8 eytotoxic T cell and foxp3 regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes[J].Breast Cancer Res Treat,2011,130(2):645-655.
[10]Nakamura T,Shima T,Saeki A,et al.Expression of indoleamine 2,3-dioxygenase and the recruitment of foxp3-expressing regulatofy T cells in the development and progression of uterine cervical cancer[J].Cancer Sci,2007,98(6):874-881.
[11]Matsuura K,Yamaguehi Y,Ueno H,et al.Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma[J].Cancer,2006,106(6):1227-1236.
[12]Su X,Ye J,Hsueh EC,et al.Tumor microenvironments direct the recruitment and expansion of human Th17 cells[J].J Immunol,2010,184(3):1630-1641.
[13]Shao SF,Yu CM.Experssion and clinical significance of Th17 and treg cells in peripheral blood of patients with ovarian cancer[J].Chinese Journal of Immunology,2015,31(4):537-540.[邵素芳,于春美.卵巢癌患者外周血Th17/Treg细胞的检测及其临床意义[J].中国免疫学杂志,2015,31(4):537-540.]
[14]Bao Z,Lu G,Cui D,et al.IL-17A-producing T cells are associated with the progression of lung adenocarcinoma[J].Oncol Rep,2016,36(2):641-650.
[15]Shaobin W,Yu X,Jiatian L,et al.Changes of CD4+T-cell subsets after radiofrequency ablation in lung cancer and its significance[J].J Cancer Res Ther,2016,12(Supplement):C166-C170.
[16]Jia HM,Fang XZ,Zhang GQ,et al.Expression of IL-17and foxp3 inⅢA stage lung squamouse cell carcinoma and adenocarcinoma and their potential relationship with prognosis of carcinoma[J].Chinese General Practice,2012,15(12):1345-1349.[贾慧民,房新志,张国庆,等.白介素17与Foxp3在ⅢA期肺鳞癌和腺癌中的表达及与预后的关系研究[J].中国全科医学,2012,15(12):1345-1349.]
[17]Guan L,Yang F,Gong Y.Expression and significance of Th17 cells in patients with malignant pleural effusion[J].Guangdong Medical Journal,2014,35(4):537-539.[官莉,杨芳,宫原.恶性胸腔积液患者Th17细胞的表达及意义[J].广东医学,2014,35(4):537-539.]
[18]Li Q,Chen J,Liu Y,et al.Prevalence of Th17 and treg cells in gastric cancer patients and its correlation with clinical parameters[J].Oncol Rep,2013,30(3):1215-1222.
[19]Zhang JP,Yan J,Xu J,et al.Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients[J].J Hepatol,2009,50(5):980-989.
[20]Decker T,Fischer G,Bücke W,et al.Increased number of regulatory T cells(tregs)in the peripheral blood of patients with her2/neu-positive early breast cancer[J].J Cancer Res Clin Oncol,2012,138(11):1945-1950.
[2]Noack M,Miossec P.Th17 and regulatory T cell balance in autoimmune and inflammatory diseases[J].Autoimmun Rev,2014,13(6):668-677.
[3]Whiteside TL.Regulatory T cell subsets in human cancer:are they regulating for or against tumor progression?[J].Cancer Immunol Immunother,2014,63(1):67-72.
[4]Fang Q,Dai AG,Jiang YL.Research progress of Th17/Treg and pulmonary diseases[J].Journal of Clinical Pulmonary Medicine,2016,21(5):899-902.[万琴,戴爱国,蒋永亮.Th17/Treg与肺部疾病的研究进展[J].临床肺科杂志,2016,21(5):899-902.]
[5]Zou Q,Yao X,Feng J,et al.Praziquantel facilitates ifngamma-producing CD8 T cells and IL-17-producing CD8T cells responses to DNA vaccination in mice[J].PLo S One,2011,6(10):e25525.
[6]Sun WH,Wei XF,Zhao P,et al.Changes in Treg cells and their cytokine production in the peripheral blood of gastric cancer patients following immunotherapy with DCCIK cells[J].Chin J Cancer Biother,2015,22(1):79-83.[孙伟红,魏晓芳,赵鹏,等.胃癌患者DC-CIK治疗前后外周血Treg细胞及相关细胞因子的变化[J].中国肿瘤生物治疗杂志,2015,22(1):79-83.]
[7]Zhen QH,Wang N,Song TJ,et al.Change of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances[J].Journal of Jilin University(Med Edition),2016,42(4):659-664.[郑全辉,王娜,宋天姣,等.肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义[J].吉林大学学报(医学版),2016,42(4):659-664.]
[8]Wang HB,Guo CL,Cheng W,et al.Analysis of Treg cells in hepatocellular carcinoma and their clinical significance[J].Journal of Chinese Oncology,2015,21(2):133-137.[王宏波,郭存丽,程文,等.肝细胞癌患者病灶局部Treg细胞分析及其临床意义[J].肿瘤学杂志,2015,21(2):133-137.]
[9]Liu F,Lang R,Zhao J,et al.CD8 eytotoxic T cell and foxp3 regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes[J].Breast Cancer Res Treat,2011,130(2):645-655.
[10]Nakamura T,Shima T,Saeki A,et al.Expression of indoleamine 2,3-dioxygenase and the recruitment of foxp3-expressing regulatofy T cells in the development and progression of uterine cervical cancer[J].Cancer Sci,2007,98(6):874-881.
[11]Matsuura K,Yamaguehi Y,Ueno H,et al.Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma[J].Cancer,2006,106(6):1227-1236.
[12]Su X,Ye J,Hsueh EC,et al.Tumor microenvironments direct the recruitment and expansion of human Th17 cells[J].J Immunol,2010,184(3):1630-1641.
[13]Shao SF,Yu CM.Experssion and clinical significance of Th17 and treg cells in peripheral blood of patients with ovarian cancer[J].Chinese Journal of Immunology,2015,31(4):537-540.[邵素芳,于春美.卵巢癌患者外周血Th17/Treg细胞的检测及其临床意义[J].中国免疫学杂志,2015,31(4):537-540.]
[14]Bao Z,Lu G,Cui D,et al.IL-17A-producing T cells are associated with the progression of lung adenocarcinoma[J].Oncol Rep,2016,36(2):641-650.
[15]Shaobin W,Yu X,Jiatian L,et al.Changes of CD4+T-cell subsets after radiofrequency ablation in lung cancer and its significance[J].J Cancer Res Ther,2016,12(Supplement):C166-C170.
[16]Jia HM,Fang XZ,Zhang GQ,et al.Expression of IL-17and foxp3 inⅢA stage lung squamouse cell carcinoma and adenocarcinoma and their potential relationship with prognosis of carcinoma[J].Chinese General Practice,2012,15(12):1345-1349.[贾慧民,房新志,张国庆,等.白介素17与Foxp3在ⅢA期肺鳞癌和腺癌中的表达及与预后的关系研究[J].中国全科医学,2012,15(12):1345-1349.]
[17]Guan L,Yang F,Gong Y.Expression and significance of Th17 cells in patients with malignant pleural effusion[J].Guangdong Medical Journal,2014,35(4):537-539.[官莉,杨芳,宫原.恶性胸腔积液患者Th17细胞的表达及意义[J].广东医学,2014,35(4):537-539.]
[18]Li Q,Chen J,Liu Y,et al.Prevalence of Th17 and treg cells in gastric cancer patients and its correlation with clinical parameters[J].Oncol Rep,2013,30(3):1215-1222.
[19]Zhang JP,Yan J,Xu J,et al.Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients[J].J Hepatol,2009,50(5):980-989.
[20]Decker T,Fischer G,Bücke W,et al.Increased number of regulatory T cells(tregs)in the peripheral blood of patients with her2/neu-positive early breast cancer[J].J Cancer Res Clin Oncol,2012,138(11):1945-1950.