The appearance of Tregs in cancer nest is a promising independent risk factor in colon cancer

被引:39
作者
Xu, Wei [1 ]
Liu, Hao [1 ]
Song, Jun [1 ]
Fu, Hai-Xiao [1 ]
Qiu, Lei [1 ]
Zhang, Bao-Fu [2 ]
Li, Hui-Zhong [2 ]
Bai, Jin [2 ]
Zheng, Jun-Nian [2 ]
机构
[1] Xuzhou Med Coll, Dept Surg, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China
[2] Xuzhou Med Coll, Jiangsu Key Lab Biol Canc Therapy, Xuzhou 221002, Jiangsu, Peoples R China
关键词
Colon carcinoma; Tregs; FOXP3; Prognostic; Tissue microarray; REGULATORY T-CELLS; COLORECTAL-CANCER; FOXP3; EXPRESSION; SURVIVAL; CARCINOMA; PROGNOSIS; MECHANISM;
D O I
10.1007/s00432-013-1500-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
To investigate the prognostic value of tumor-infiltrating regulatory T cells (Tregs) in the distribution of cancer nest, cancer stroma and normal mucosa and FOXP3-positive cancer cells in colon cancer patients after resection. Paraffin blocks of operation resection of primary adenocarcinoma of colon were obtained from ninety patients. The distribution of tumor-infiltrating Tregs was detected by tissue microarray and immunohistochemistry staining technique to evaluate the prognostic effects by Kaplan-Meier and Cox regression analysis using median values as cutoff. The intratumoral Tregs counts were significantly higher than that in corresponding normal mucosa tissues (P < 0.001); the Tregs counts in cancer nest were significantly lower than that in corresponding cancer stroma tissues (P < 0.001); the increased intratumoral Tregs counts were associated with favorable prognosis (P < 0.05); the presence of Tregs in cancer nest was associated with unfavorable prognosis and was an independent prognostic factor for overall survival (P < 0.05). The appearance of FOXP3-positive cancer cells was associated with worse prognosis (P < 0.05). In addition, the frequency of the presence of FOXP3-positive cancer cells was higher in patients with lymphatic invasion (P < 0.001) and lower in patients with early TNM stage (P < 0.01). The higher tumor-infiltrating Tregs counts are closely associated with the improved prognostic effects of colon carcinoma. Tregs play different roles in cancer nest and cancer stroma. And the appearance of Tregs in cancer nest is a promising independent risk factor for overall survival in colon carcinoma. FOXP3-positive cancer cells may also be a risk factor for overall survival in colon carcinoma.
引用
收藏
页码:1845 / 1852
页数:8
相关论文
共 27 条
[1]
Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse [J].
Bates, Gaynor J. ;
Fox, Stephen B. ;
Han, Cheng ;
Leek, Russell D. ;
Garcia, Jose F. ;
Harris, Adrian L. ;
Banham, Alison H. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (34) :5373-5380
[2]
Inflammation and Cancer: IL-6 and STAT3 Complete the Link [J].
Bromberg, Jacqueline ;
Wang, Timothy C. .
CANCER CELL, 2009, 15 (02) :79-80
[3]
CD4+ CD25+ FOXP3+ Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer [J].
Clarke, Sarah L. ;
Betts, Gareth J. ;
Plant, Andrea ;
Wright, Kate L. ;
El-Shanawany, Tariq M. ;
Harrop, Richard ;
Torkington, Jared ;
Rees, Brian I. ;
Williams, Geraint T. ;
Gallimore, Awen M. ;
Godkin, Andrew J. .
PLOS ONE, 2006, 1 (02)
[4]
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[5]
High frequency of tumor-infiltrating FOXP3+ regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients [J].
Frey, Daniel M. ;
Droeser, Raoul A. ;
Viehl, Carsten T. ;
Zlobec, Inti ;
Lugli, Alessandro ;
Zingg, Urs ;
Oertli, Daniel ;
Kettelhack, Christoph ;
Terracciano, Luigi ;
Tornillo, Luigi .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (11) :2635-2643
[6]
The adaptive immunologic microenvironment in colorectal cancer:: A novel perspective [J].
Galon, Jerome ;
Fridman, Wolf-Herman ;
Pages, Franck .
CANCER RESEARCH, 2007, 67 (05) :1883-1886
[7]
Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection [J].
Gao, Qiang ;
Qiu, Shuang-Jian ;
Fan, Jia ;
Zhou, Jian ;
Wang, Xiao-Ying ;
Xiao, Yong-Sheng ;
Xu, Yang ;
Li, Yi-Wei ;
Tang, Zhao-You .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (18) :2586-2593
[8]
Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer [J].
Hinz, Sebastian ;
Pagerols-Raluy, Laia ;
Oberg, Hans-Heinrich ;
Ammerpohl, Ole ;
Gruessel, Sandra ;
Sipos, Bence ;
Gruetzmann, Robert ;
Pilarskys, Christian ;
Ungefroren, Hendrik ;
Saeger, Hans-Detlev ;
Mloeppel, Guenter ;
Kabelitz, Dieter ;
Kalthoff, Holger .
CANCER RESEARCH, 2007, 67 (17) :8344-8350
[9]
Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinorna and its premalignant lesions [J].
Hiraoka, Nobuyoshi ;
Onozato, Kaoru ;
Kosuge, Tomoo ;
Hirohashi, Setsuo .
CLINICAL CANCER RESEARCH, 2006, 12 (18) :5423-5434
[10]
Control of regulatory T cell development by the transcription factor Foxp3 [J].
Hori, S ;
Nomura, T ;
Sakaguchi, S .
SCIENCE, 2003, 299 (5609) :1057-1061