Full Text:   <2615>

Summary:  <1760>

CLC number: R735

On-line Access: 2016-12-05

Received: 2016-06-25

Revision Accepted: 2016-08-26

Crosschecked: 2016-11-10

Cited: 2

Clicked: 4610

Citations:  Bibtex RefMan EndNote GB/T7714


Ai-bin Zhang


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.12 P.984-991


Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

Author(s):  Ai-bin Zhang, Yi-gang Qian, Shu-sen Zheng

Affiliation(s):  Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   shusenzheng@zju.edu.cn

Key Words:  Hepatocellular carcinoma, Regulatory T cells, Prognosis

Ai-bin Zhang, Yi-gang Qian, Shu-sen Zheng. Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma[J]. Journal of Zhejiang University Science B, 2016, 17(12): 984-991.

@article{title="Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma",
author="Ai-bin Zhang, Yi-gang Qian, Shu-sen Zheng",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma
%A Ai-bin Zhang
%A Yi-gang Qian
%A Shu-sen Zheng
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 12
%P 984-991
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600264

T1 - Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma
A1 - Ai-bin Zhang
A1 - Yi-gang Qian
A1 - Shu-sen Zheng
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 12
SP - 984
EP - 991
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600264

We investigated the prognostic role of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC). Relevant evidence regarding prognostic significance of Tregs was systematically searched in MEDLINE and Embase databases. A meta-analysis was performed to compare survival in patients with high or low Tregs level (either in peripheral blood or tumor). Eighteen studies were identified that fulfilled for the eligibility criteria and were included for data synthesis. Our pooled hazard ratios (HRs) demonstrated that increased Tregs intratumoral accumulation was significantly associated with worse overall survival (HR=2.04, 95% confidence interval (CI): 1.72–2.42) and disease-free survival (HR=1.82, 95% CI: 1.58–2.09). Three studies evaluated the role of Tregs in peripheral blood, and all of them showed that increased peripheral Tregs correlated with shortened disease-free and overall survival. Collectively, our results showed that the increased Tregs count is tightly associated with the shortened survivals. Its measurement in either primary tumor or even circulation might be a candidate marker of prognostic significance in HCC patients.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Cai, M.Y., Xu, Y.F., Qiu, S.J., et al., 2009. Human leukocyte antigen-G protein expression is an unfavorable prognostic predictor of hepatocellular carcinoma following curative resection. Clin. Cancer Res., 15(14):4686-4693.

[2]Chen, K.J., Lin, S.Z., Zhou, L., et al., 2011. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS ONE, 6(9):e24671.

[3]Das, S.L., Singh, P.P., Phillips, A.R., et al., 2014. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut, 63(5):818-831.

[4]Fu, J., Xu, D., Liu, Z., et al., 2007. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology, 132(7):2328-2339.

[5]Gao, Q., Qiu, S.J., Fan, J., et al., 2007. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol., 25(18):2586-2593.

[6]Gao, Q., Wang, X.Y., Qiu, S.J., et al., 2009. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin. Cancer Res., 15(3):971-979.

[7]Hernandez-Gea, V., Toffanin, S., Friedman, S.L., et al., 2013. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology, 144(3):512-527.

[8]Huang, Y., Wang, F.M., Wang, T., et al., 2012. Tumor-infiltrating FoxP3+ Tregs and CD8+ T cells affect the prognosis of hepatocellular carcinoma patients. Digestion, 86(4):329-337.

[9]Jemal, A., Bray, F., Center, M.M., et al., 2011. Global cancer statistics. CA Cancer J. Clin., 61(2):69-90.

[10]Ju, M.J., Qiu, S.J., Fan, J., et al., 2009a. Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection. Am. J. Clin. Pathol., 131(4):498-510.

[11]Ju, M.J., Qiu, S.J., Gao, Q., et al., 2009b. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci., 100(7):1267-1274.

[12]Kobayashi, N., Hiraoka, N., Yamagami, W., et al., 2007. FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin. Cancer Res., 13(3):902-911.

[13]Lan, X,P., Chen, Y.G., Wang, Z., et al., 2015. mmunotherapy of DC-CIK cells enhances the efficacy of chemotherapy for solid cancer: a meta-analysis of randomized controlled trials in Chinese patients. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 16(2):743-756.

[14]Lin, S.Z., Chen, K.J., Xu, Z.Y., et al., 2013. Prediction of recurrence and survival in hepatocellular carcinoma based on two Cox models mainly determined by FoxP3+ regulatory T cells. Cancer Prev. Res. (Phila), 6(6):594-602.

[15]Mathai, A.M., Kapadia, M.J., Alexander, J., et al., 2012. Role of Foxp3-positive tumor-infiltrating lymphocytes in the histologic features and clinical outcomes of hepatocellular carcinoma. Am. J. Surg. Pathol., 36(7):980-986.

[16]Ormandy, L.A., Hillemann, T., Wedemeyer, H., et al., 2005. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res., 65(6):2457-2464.

[17]Peng, G., Li, S., Wu, W., et al., 2008. Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection. Immunology, 123(1):57-65.

[18]Poon, R.T.P., Fan, S.T., Wong, J., 2000. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann. Surg., 232(1):10-24.

[19]Sakaguchi, S., 2000. Regulatory T cells: key controllers of immunologic self-tolerance. Cell, 101(5):455-458.

[20]Sasaki, A., Tanaka, F., Mimori, K., et al., 2008. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in patients with hepatocellular carcinoma. Eur. J. Surg. Oncol., 34(2):173-179.

[21]Schoenleber, S.J., Kurtz, D.M., Talwalkar, J.A., et al., 2009. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br. J. Cancer, 100(9):1385-1392.

[22]Shen, S.L., Liang, L.J., Peng, B.G., et al., 2011. Foxp3+ regulatory T cells and the formation of portal vein tumour thrombus in patients with hepatocellular carcinoma. Can. J. Surg., 54(2):89-94.

[23]Shevach, E.M., 2002. CD4+CD25+ suppressor T cells: more questions than answers. Nat. Rev. Immunol., 2(6):389-400.

[24]Stross, L., Gunther, J., Gasteiger, G., et al., 2012. Foxp3+ regulatory T cells protect the liver from immune damage and compromise virus control during acute experimental hepatitis B virus infection in mice. Hepatology, 56(3):873-883.

[25]Tierney, J.F., Stewart, L.A., Ghersi, D., et al., 2007. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 8(1):16.

[26]Unitt, E., Rushbrook, S.M., Marshall, A., et al., 2005. Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology, 41(4):722-730.

[27]Wang, F., Jing, X., Li, G., et al., 2012. Foxp3+ regulatory T cells are associated with the natural history of chronic hepatitis B and poor prognosis of hepatocellular carcinoma. Liver Int., 32(4):644-655.

[28]Will, B., Steidl, U., 2014. Stem cell fate regulation by dynein motor protein Lis1. Nat. Genet., 46(3):217-218.

[29]Xu, D., Fu, J., Jin, L., et al., 2006. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J. Immunol., 177(1):739-747.

[30]Zhou, J., Ding, T., Pan, W., et al., 2009. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int. J. Cancer, 125(7):1640-1648.

[31]Zhou, L., Fu, J.L., Lu, Y.Y., et al., 2010. Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma. J. Gastroenterol., 45(9):968-978.

Open peer comments: Debate/Discuss/Question/Opinion


Abay Alebachew@Mr<abayg2002@yahoo.com>

2016-12-07 18:55:07

I want to published my Thesis Paper . the title of my thesis paper is Assessment of Job satistisfacation.

Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE