首页 » 文章 » 文章详细信息
Cancer Science Volume 110 ,Issue 7 ,2019-06-28
Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer
ORIGINAL ARTICLES
Li Song 1 , 2 , 3 Shoubao Ma 4 , 5 Longpei Chen 6 Liyan Miao 1 Min Tao 7 , 8 Haiyan Liu 9
Show affiliations
DOI:10.1111/cas.14068
Received 2018-12-06, accepted for publication 2019-05-01, Published 2019-05-01
PDF
摘要

Abstract The presence of interleukin (IL)‐17‐producing T cells has recently been reported in non‐small cell lung cancer (NSCLC) patients. However, the long‐term prognostic significance of these populations in NSCLC patients remains unknown. In the present study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NC). Percentages of IL‐17‐producing CD4+T (Th17), CD8+T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC. All NSCLC patients were followed up until July 2018. Median follow‐up time was 13.5 months (range 1‐87 months). The 3‐ and 5‐year survival rate was 27% and 19.6%, respectively. We found that Th17 cells and γδT17 cells were significantly increased, whereas Tc17 cells were markedly decreased in patients with NSCLC compared with those in NC. In addition, Th17 cells were significantly positively associated with T helper type 1 cells (Th1), whereas γδT17 cells were significantly negatively associated with γδT + interferon (IFN)‐γ+ cells. High percentages of peripheral Tc17 cells were significantly associated with favorable 5‐year OS (P = .025), especially in patients with early TNM stage (P = .016). Furthermore, high percentages of peripheral Th17 cells were positively associated with favorable 5‐year OS in patients with late TNM stage (P = .002). However, no significant association was observed between γδT17 cells and OS, regardless of the TNM stage. In conclusion, our findings suggest that enhanced Th17 and reduced Tc17 cells in the peripheral blood could be a significant predictor of a favorable prognosis for NSCLC patients.

关键词

Th17 cell;Tc17 cell;NSCLC;IL;γδT17 cell

授权许可

© 2019 Japanese Cancer Association

图表
通讯作者

1. Min Tao.Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China;PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, China.taomin@suda.edu.cn
2. Haiyan Liu.Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore.taomin@suda.edu.cn

推荐引用方式

Li Song,Shoubao Ma,Longpei Chen,Liyan Miao,Min Tao,Haiyan Liu. Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer. Cancer Science ,Vol.110, Issue 7(2019)

您觉得这篇文章对您有帮助吗?
分享和收藏
0

是否收藏?

参考文献
[1] Ye ZJ, Zhou Q, Gu YY, et al. Generation and differentiation of IL‐17‐producing CD4+ T cells in malignant pleural effusion. J Immunol. 2010;185(10):6348‐6354.
[2] Muranski P, Borman ZA, Kerkar SP, et al. Th17 cells are long lived and retain a stem cell‐like molecular signature. Immunity. 2011;35(6):972‐985.
[3] Colonna M. Innate lymphoid cells: diversity, plasticity, and unique functions in immunity. Immunity. 2018;48(6):1104‐1117.
[4] Yang G, Li H, Yao Y, Xu F, Bao Z, Zhou J. Treg/Th17 imbalance in malignant pleural effusion partially predicts poor prognosis. Oncol Rep. 2015;33(1):478‐484.
[5] Muranski P, Boni A, Antony PA, et al. Tumor‐specific Th17‐polarized cells eradicate large established melanoma. Blood. 2008;112(2):362‐373.
[6] Zhang JP, Yan J, Xu J, et al. Increased intratumoral IL‐17‐producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol. 2009;50(5):980‐989.
[7] Wang JT, Li H, Zhang H, et al. Intratumoral IL17‐producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer. Ann Oncol. 2019;30(2):266‐273.
[8] Tosolini M, Kirilovsky A, Mlecnik B, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 2011;71(4):1263‐1271.
[9] Du R, Zhao H, Yan F, Li H. IL‐17+Foxp3+ T cells: an intermediate differentiation stage between Th17 cells and regulatory T cells. J Leukoc Biol. 2014;96(1):39‐48.
[10] Xu C, Yu L, Zhan P, Zhang Y. Elevated pleural effusion IL‐17 is a diagnostic marker and outcome predictor in lung cancer patients. Eur J Med Res. 2014;19:23.
[11] Ma C, Dong X. Colorectal cancer‐derived Foxp3(+) IL‐17(+) T cells suppress tumour‐specific CD8+ T cells. Scand J Immunol. 2011;74(1):47‐51.
[12] Ma S, Cheng Q, Cai Y, et al. IL‐17A produced by gammadelta T cells promotes tumor growth in hepatocellular carcinoma. Cancer Res. 2014;74(7):1969‐1982.
[13] Tajima M, Wakita D, Satoh T, Kitamura H, Nishimura T. IL‐17/IFN‐gamma double producing CD8+ T (Tc17/IFN‐gamma) cells: a novel cytotoxic T‐cell subset converted from Tc17 cells by IL‐12. Int Immunol. 2011;23(12):751‐759.
[14] Liu J, Duan Y, Cheng X, et al. IL‐17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun. 2011;407(2):348‐354.
[15] Kondo T, Takata H, Matsuki F, Takiguchi M. Cutting edge: phenotypic characterization and differentiation of human CD8+ T cells producing IL‐17. J Immunol. 2009;182(4):1794‐1798.
[16] Bao Z, Lu G, Cui D, Yao Y, Yang G, Zhou J. IL‐17A‐producing T cells are associated with the progression of lung adenocarcinoma. Oncol Rep. 2016;36(2):641‐650.
[17] Lee MH, Tung‐Chieh Chang J, Liao CT, Chen YS, Kuo ML, Shen CR. Interleukin 17 and peripheral IL‐17‐expressing T cells are negatively correlated with the overall survival of head and neck cancer patients. Oncotarget. 2018;9(11):9825‐9837.
[18] Numasaki M, Watanabe M, Suzuki T, et al. IL‐17 enhances the net angiogenic activity and in vivo growth of human non‐small cell lung cancer in SCID mice through promoting CXCR‐2‐dependent angiogenesis. J Immunol. 2005;175(9):6177‐6189.
[19] Chien YH, Zeng X, Prinz I. The natural and the inducible: interleukin (IL)‐17‐producing gammadelta T cells. Trends Immunol. 2013;34(4):151‐154.
[20] Curtis MM, Way SS, Wilson CB. IL‐23 promotes the production of IL‐17 by antigen‐specific CD8 T cells in the absence of IL‐12 and type‐I interferons. J Immunol. 2009;183(1):381‐387.
[21] O'Brien RL, Roark CL, Born WK. IL‐17‐producing gammadelta T cells. Eur J Immunol. 2009;39(3):662‐666.
[22] Pan B, Che D, Cao J, et al. Interleukin‐17 levels correlate with poor prognosis and vascular endothelial growth factor concentration in the serum of patients with non‐small cell lung cancer. Biomarkers. 2015;20(4):232‐239.
[23] Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6(11):1133‐1141.
[24] Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(6):1141‐1149.
[25] Bao Y, Guo L, Mo J. Characterization of gammadelta T cells in patients with non‐small cell lung cancer. Oncol Lett. 2017;14(1):1133‐1140.
[26] He S, Fei M, Wu Y, et al. Distribution and clinical significance of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients. Int J Mol Sci. 2011;12(11):7424‐7437.
[27] Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17‐producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123‐1132.
[28] Wu P, Wu D, Ni C, et al. gammadeltaT17 cells promote the accumulation and expansion of myeloid‐derived suppressor cells in human colorectal cancer. Immunity. 2014;40(5):785‐800.
[29] Silva‐Santos B, Serre K, Norell H. gammadelta T cells in cancer. Nat Rev Immunol. 2015;15(11):683‐691.
[30] Ma Y, Aymeric L, Locher C, et al. Contribution of IL‐17‐producing gamma delta T cells to the efficacy of anticancer chemotherapy. J Exp Med. 2011;208(3):491‐503.
[31] Jiang G, Ma S, Wei Y, Wu Y, Yu X, Liu H. The prevalence and distribution of Th17 and Tc17 cells in patients with thyroid tumor. Immunol Lett. 2014;162(1 Pt A):68‐73.
[32] Tian X, Ma J, Wang T, et al. Long non‐coding RNA RUNXOR accelerates MDSC‐mediated immunosuppression in lung cancer. BMC Cancer. 2018;18(1):660.
[33] Martin‐Orozco N, Muranski P, Chung Y, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 2009;31(5):787‐798.
[34] Numasaki M, Fukushi J, Ono M, et al. Interleukin‐17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620‐2627.
[35] Zhang GQ, Han F, Fang XZ, Ma XM. CD4+, IL17 and Foxp3 expression in different pTNM stages of operable non‐small cell lung cancer and effects on disease prognosis. Asian Pac J Cancer Prev. 2012;13(8):3955‐3960.
[36] Powell JW, Dexter E, Scalzetti EM, Bogart JA. Treatment advances for medically inoperable non‐small‐cell lung cancer: emphasis on prospective trials. Lancet Oncol. 2009;10(9):885‐894.
[37] Ostrand‐Rosenberg S. Tolerance and immune suppression in the tumor microenvironment. Cell Immunol. 2016;299:23‐29.
[38] Kuang DM, Peng C, Zhao Q, et al. Tumor‐activated monocytes promote expansion of IL‐17‐producing CD8+ T cells in hepatocellular carcinoma patients. J Immunol. 2010;185(3):1544‐1549.
[39] Lu L, Pan K, Zheng HX, et al. IL‐17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival. J Immunother. 2013;36(8):451‐458.
[40] Kryczek I, Wei S, Szeliga W, Vatan L, Zou W. Endogenous IL‐17 contributes to reduced tumor growth and metastasis. Blood. 2009;114(2):357‐359.
[41] Chen X, Wan J, Liu J, et al. Increased IL‐17‐producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer. 2010;69(3):348‐354.
[42] Benchetrit F, Ciree A, Vives V, et al. Interleukin‐17 inhibits tumor cell growth by means of a T‐cell‐dependent mechanism. Blood. 2002;99(6):2114‐2121.
[43] Kotsakis A, Koinis F, Katsarou A, et al. Prognostic value of circulating regulatory T cell subsets in untreated non‐small cell lung cancer patients. Sci Rep. 2016;6:39247.
[44] Xu C, Hao K, Yu L, Zhang X. Serum interleukin‐17 as a diagnostic and prognostic marker for non‐small cell lung cancer. Biomarkers. 2014;19(4):287‐290.
[45] Zhukovsky M, Varaksin A, Pakholkina O. Statistical analysis of observational study of the influence of radon and other risk factors on lung cancer incidence. Radiat Prot Dosimetry. 2014;160(1–3):108‐111.
[46] Hinrichs CS, Kaiser A, Paulos CM, et al. Type 17 CD8+ T cells display enhanced antitumor immunity. Blood. 2009;114(3):596‐599.
[47] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7‐30.