Similar articles

Abstract: 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.

调节性T细胞在肝癌患者中的预后意义

[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.