|Table of Contents|

The investigation of regulatory role of immune factors FoxP3,CCL22 and CCR4 in the microenvironment of cervical cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2019 02
Page:
192-195
Research Field:
Publishing date:

Info

Title:
The investigation of regulatory role of immune factors FoxP3,CCL22 and CCR4 in the microenvironment of cervical cancer
Author(s):
Zhao Minyi1; Zhang Qian2; Wei Xing1; Li Yang1; Cao Di1; Yang Xuemei3; Quan Shimin1; Jia Hongran2; Zhang Wenke4; Yang Xiaofeng1
1.Department of Obstetrics and Gynecology,First Affiliated Hospital of Xi'an Jiaotong University，Shaanxi Xi'an 710061,China;2.Northwest Women and Children's Hospital，Shaanxi Xi'an 710061,China；3.The Tumor Hospital of Shaanxi Province，Shaanxi Xi'an 710061,China；4.The Affiliated Hospital of Qingdao University，Shandong Qingdao 266555,China.
Keywords:
cervical cancer; immune microenvironment; Foxp3; CCL22; CCR4
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2019.02.003
Abstract:
Objective:To explore the expression and correlation of FoxP3，CCL22 and CCR4 in cervical carcinoma，therefore to dig their immunomodulatory role in local site of cervical cancer.Methods:Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix tissues were enrolled in this study.Real-time Polymerase Chain Reaction was performed to profile the mRNA expression pattern of FoxP3,CCL22 and CCR4 in these samples.Results:FoxP3 and CCL22 mRNAs expression in normal cervix was lower than that in neoplastic foci and pericarcinous tissues.The expression level of CCR4 mRNA in neoplastic foci was higher than that in pericarcinous tissues and normal cervix.The mRNA expression of FoxP3 and CCL22 was increased in HPV-positive neoplastic foci and pericarcinous tissues while CCR4 seemed invariable regardless of different HPV infection status.Compared to low grade squamous cell carcinoma,the mRNA of FoxP3,CCL22 and CCR4 increased moderately in high grade leisions.The pair wise positive correlations were exhibited in both neoplastic foci and pericarcinous tissues among the mRNA expression level of these three factors.Conclusion:In microenvironment of cervical cancer,FoxP3,CCL22 and CCR4 may exert an influence on down-regulating immune response and the positive relevance among these three factors implies that they may synergistically promote immunosuppression,thus deteriorating the disequilibrium of local immune status.

References:

［1］Wu H,Zhang J.miR-124 rs531564 polymorphism influences genetic susceptibility to cervical cancer［J］.Int J Clin Exp Med,2014,7(12):5847-5851.
［2］Stanley MA.Immune responses to human papilloma viruses［J］.Indian J Med Res,2009,130(3):266-276.
［3］Dunn GP,Old LJ,Schreiber RD.The three Es of cancer immunoediting［J］.Annu Rev Immunol,2004,22:329-360.
［4］Zhang Y，Ding AP.Correlation state of HPV-16 existential status with Th17/Treg cytokine［J］.National Medical Journal of China,2013,93(37):2957-2960.
［5］Uhlig HH,Coombes J,Mottet C,et al.Characterization of FoxP3(+)CD4(+)CD25(+) and IL-10-secreting CD4(+)CD25(+) T cells during cure of colitis［J］.Journal of Immunology,2006,177(9):5852-5860.
［6］Collison LW,Workman CJ,Kuo TT,et al.The inhibitory cytokine IL-35 contributes to regulatory T-cell function［J］.Nature,2007,450(7169):566-569.
［7］Hori S,Nomura T,Sakaguchi S.Control of regulatory T cell development by the transcription factor FoxP3［J］.Science,2003,299(5609):1057-1061.
［8］Fontenot JD,Gavin MA,Rudensky AY.FoxP3 programs the development and function of CD4+CD25+ regulatory T cells［J］.Nat Immunol,2003,4(4):330-336.
［9］Li YQ,Liu FF,Zhang XM,et al.Tumor secretion of CCL22 activates intratumoral Treg infiltration and is independent prognostic predictor of breast cancer［J］.PLoS One,2013,8(10):e76379.
［10］Kurman RJ,Carcangiu ML,Herrington CS,et al.WHO classification of tumors of female reproductive organs［M］.Lyon:IARC Press,2014:179.
［11］Kim M,Grimmig T,Grimm M,et al.Expression of FoxP3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer［J］.PLoS One,2013,8(1):e53630.
［12］De Reuver PR,Mehta S,Gill P,et al.Immunoregulatory forkhead box protein p3-positive lymphocytes are associated with overall survival in patients with pancreatic neuroendocrine tumors［J］.J Am Coll Surg,2016,223(3):281-287.
［13］Lin SZ,Chen KJ,Xu ZY,et al.Prediction of recurrence and survial in hepatocellular carcinoma based on two Cox models mainly determined by FoxP3+ regulatory T cells［J］.Cancer Prev Res(Phila),2013,6(6):594-602.
［14］Winkler I,Wilczynska B,Bojarska-Junak A,et al.Regulatory T lymphocytes and transforming growth factor beta in epithelial ovarian tumors-prognostic significance［J］.J Ovarian Res,2015,8:39.
［15］Luo Q,Jin Z,Chen S,et al.Changes of TRGV genes and prognosis-related chemokine/receptor gene expressions in T cell lymphoma［J］.Chin J Cell Mol Imm,2017,33(3):362-366.
［16］Nakamura ES,Koizumi K,Kobayashi M,et al.RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4［J］.Clin Exp Metastasis,2006,23 (1):9-18.
［17］Gobert M,Treilleux I,Bendriss-Vermare N,et al.Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome［J］.Cancer Res,2009,69(5):2000-2009.
［18］Gong SC,Zhang HD,Xing GQ,et al.The role of CD 4+CD25+T regs and CCL17,CCL22 in the pathogenesis of head and neck squamous cell carcinoma［J］.Journal of Clinical Otorhinolarynogology Head and Neck Surgery,2017,31(20):1557-1560.
［19］Woo YL,van den Hende M,Sterling JC,et al.A prospective study on the natural course of low-grade aquamous intraepithelial lesions and the presence of HPV16 E2,E6 and E7-specific T-cell responses［J］.Int J Cancer,2010,126(1):133-141.
［20］Ghosh A,Dasgupta A,Ghosh T,et al.A study of the expression and localization of toll-like receptors 2 and 9 in different grades of cervical intraepithelial neoplasia and squamous cell carcinoma［J］.Exp Mol Patho,2015,99(3):720-724.
［21］Chiantore MV,Mangino G,Luliano M,et al.IFN-β antiproliferative effect and miRNA regulation in human papilloma virus E6- and E7-transfected keratinocyte［J］.Cytokine,2015,89:235-238.
［22］Barros MR,De Oliveira THA,De Melo CML,et al.Viral modulation of TLRs and cytokines and the related immunotherapies for HPV-associated cancers［J］.J Immunol Res,2018,2018:2912671.

Memo

Memo:
National Natural Science Foundation of China(No.81472428);国家自然科学基金面上项目（编号：81472428）
Last Update: 1900-01-01