Quantity and Function of CD4+CD25+FOXP3+ Regulatory T Cell Decreased after Operation in Hepatocarcinoma Patients_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Xuefan ¹ , JIANG Xiaofeng ¹ , FU Qingcai ² , LIN Lin ¹ , WEI Yuntao ² , GUO Dawei ¹ , LIANG Jian. ¹

1.Department of General Surgery， The Fourth Affiliated Hospital of China Medical University, Shenyang 110032， Liaoning Province， China;;
2.Department of Oncology Surgery， Liaoning Cancer Hospital and Institute， Shenyang 110042， Liaoning Province， China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Regulatory T Cell; Immune regulatory; FOXP3

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ObjectiveThrough the analysis of quantitative and functional changes in peripheral blood CD4+ CD25+FOXP3+ regulatory T cells (Treg) of early HCC patients before and after operation, to discuss the operation effect on the immune function from the aspect of immune suppression. MethodsExtracted the lymphocytes of peripheral blood in HCC patients before and after operation (case group, n=15) and normal people (control group, n=5 cases), and analyze the number and function of Treg by flow cytometer after extracellular (CD4, CD25) and intracellular (FOXP3) staining. ResultsCD4+CD25+ T cells and CD25+FOXP3+ T cells in preoperative peripheral blood in case group were significantly higher than those in control group (12.43±2.57)% vs. (5.56±1.02)%, (5.14±1.4)% vs. (2.18±0.83)%, P lt;0.05). These two cells decreased at 1 week after operation. 〔(10.56±2.13)%, (4.28±1.08)%〕, but there was not statistically significant (P gt;0.05), they decreased significantly at 2 weeks after operation 〔(7.30±0.89)%, (3.43±0.83)%， P lt;0.05〕. CD8+ T cells and CD4+CD25- T cells in preoperative peripheral blood in case group were significantly lower than those in control group 〔（23.42±1.80）% vs. （29.22±2.26）%，（36.14±1.12）% vs. （43.69±2.78）%， P lt;0.05〕， These two cells decreased significantly at 2 weeks after operation 〔（27.15±1.71）%，（40.30±2.00）%〕. The analysis on the Treg and AFP correlation found that they have low correlation (r=048, P lt;0.05 ). ConclusionsThe hepatectomy can improve the immune response of HCC patient. Treg may have a certain auxiliary significance in the diagnosis, treatment and prognosis of patients with hepatocellular carcinoma.

Citation： WANG Xuefan,JIANG Xiaofeng,FU Qingcai,LIN Lin,WEI Yuntao,GUO Dawei,LIANG Jian.. Quantity and Function of CD4+CD25+FOXP3+ Regulatory T Cell Decreased after Operation in Hepatocarcinoma Patients. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(11): 1180-1183. doi: Copy

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13.	Yoshizawa K, Abe H, Kubo Y, et al. Expansion of CD4+CD25+FoxP3+ regulatory T cells in hepatitis C virusrelated chronic hepatitis, cirrhosis and hepatocellular carcinoma [J]. Hepatol Res， 2010, 40(2): 179187.
14.	Gao YW, Chen YX, Wang ZM. Increased expression of cyclooxygenase2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma [J]. Digestion, 2009, 79(3): 169176.
15.	Koido S, Homma S, Hara E, et al. In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells [J]. J Transl Med, 2008, 15, 6: 51.
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19.	姜晓峰，王学范，崔哲铭，等. CD4+CD25+调节性T细胞在维持小鼠肝脏移植自发性免疫耐受状态中的作用 [J]. 中国普外基础与临床杂志， 2011， 18(4)： 366369.

1. Llovet JM, Burroughs A, Bruix J, et al. Hepatocellular carcinoma [J]. Lancet, 2003, 362（9399）: 19071917.
2. Noritoshi K, Nobuyoshi H, Wataru Y, et al. FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis [J]. Clin Cancer Res, 2007, 13(3): 902911.
3. Morse MA, Clay TM, Mosca P, et al. Immunoregulatory T cells in cancer immunotherapy [J]. Expert Opin Biol Ther, 2002， 2（8）: 827834.
4. Randolph DA, Fathman CG. Garrison FC. CD4+CD25+ regulatory T cells and their therapeutic potential [J]. Annu Rev Med, 2006, 57: 381402.
5. Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma [J]. Commentary JNCI, 2008, 100(10): 698711.
6. Waldmann TA. Effective cancer therapy through immunomodulation [J]. Annu Rev Med, 2006, 57: 6581.
7. Fu JL, Xu DP, Liu ZW, et al. Increased regulatory T cells correlate with CD8 Tcell impairment and poor survival in hepatocellular carcinoma patients [J]. Gastroenterology, 2007, 132(7): 23282339.
8. 冉江华, 李立, 陆晓青, 等. 原发性肝癌患者手术前后细胞免疫指标的变化 [J]. 临床肿瘤学杂志, 2001, 6(3): 212214.
9. 彭启全, 李升平, 徐立, 等. 117例肝癌患者外周血调节T细胞水平及其临床意义 [J]. 癌症, 2007, 26(7): 748751.
10. 林琳，梁健，马作红，等. 胰十二指肠切除术对胰头癌患者CD4+CD25+调节性T细胞的影响及临床意义 [J]. 中国普外基础与临床杂志， 2011， 18(1)： 5154.
11. Sasada T, Kimura M, Yoshida Y, et al. CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression [J]. Cancer, 2003, 98(5): 10891099.
12. Feng X, Li B, Ye H, et al. Increased frequency of CD4+CD25highFoxP3+ regulatory T cells in patients with hepatocellular carcinoma [J]. Arch Immunol Ther Exp (Warsz), 2011, 59(4): 309314.
13. Yoshizawa K, Abe H, Kubo Y, et al. Expansion of CD4+CD25+FoxP3+ regulatory T cells in hepatitis C virusrelated chronic hepatitis, cirrhosis and hepatocellular carcinoma [J]. Hepatol Res， 2010, 40(2): 179187.
14. Gao YW, Chen YX, Wang ZM. Increased expression of cyclooxygenase2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma [J]. Digestion, 2009, 79(3): 169176.
15. Koido S, Homma S, Hara E, et al. In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells [J]. J Transl Med, 2008, 15, 6: 51.
16. Butterfield LH, Ribas A. Immunotherapy of hepatocellular carcinoma [J]. Expert Opinion on Biological Therapy, 2002, 2(2): 123133.
17. Meng WS, Butterfield LH, Ribas A, et al. AlphaFetoproteinspecific tumor immunity induced by plasmid primeadenovirus boost genetic vaccination [J]. Cancer Res, 2001, 61(24): 87828786.
18. Cao M, Cabrera R, Xu Y, et al. Hepatocellular carcinoma cell supernatants increase expansion and function of CD4+CD25+ regulatory T cells [J]. Lab Invest, 2007, 87(6): 582590.
19. 姜晓峰，王学范，崔哲铭，等. CD4+CD25+调节性T细胞在维持小鼠肝脏移植自发性免疫耐受状态中的作用 [J]. 中国普外基础与临床杂志， 2011， 18(4)： 366369.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Quantity and Function of CD4+CD25+FOXP3+ Regulatory T Cell Decreased after Operation in Hepatocarcinoma Patients

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