The Expression and Significance of Helper T Lymphocyte 1 and 2 Type Cytokines before and after Breast Cancer Surgery_West China Medical Journal

Authors：

YUE Yanhong ¹ ,  SUN Zhijun ²

1. Department of General Surgery, Traditional Hospital of Meishan, Meishan, Sichuan 620010, P. R. China; 2. Department of General Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;

Corresponding author：

SUN Zhijun, Email: yyhxj1977@sohu.com

Keywords：

乳腺癌; 细胞因子; 辅助性T淋巴细胞1; 辅助性T淋巴细胞2; 手术前后; 检测

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【摘要】　目的　观察手术前后乳腺癌患者体内辅助性T淋巴细胞（helper T lymphocyte，Th） 1、2型细胞因子的表达及意义。　方法　 2009年11月－2010年12月，采用酶联免疫吸附试验检测40例乳腺癌患者（乳腺癌组）手术前、后和15例健康妇女（正常对照组）外周血单个核细胞培养上清液中Thl型细胞因子[白细胞介素（interleukin，IL）-2、干扰素（interferon，IFN）-γ]和Th2型细胞因子（IL-4、IL-6）表达水平。　结果　乳腺癌组术前外周血IL-2、IFN-γ、IL-4和IL-6的检测结果在分别为（326.5±67.4）、（288.5±35.6）、（41.2±10.8）、（526.1±136.4） ng/L，手术后分别为（958.1±284.7）、（559.6±106.9）、（26.1± 8.7）、（395.6±125.9） ng/L；在正常对照组分别为（1 498.0±325.9）、（784.6±126.3）、（16.6± 3.7）、（297.4± 83.7） ng/L。与正常对照组相比，术前乳腺癌患者外周血Th1型细胞因子表达降低，Th2型细胞因子表达升高，差异有统计学意义（P lt;0.05）；与术前相比，乳腺癌患者术后Thl型细胞因子表达升高，Th2型细胞因子表达降低，差异有统计学意义（P lt;0.05）。　结论　 ①乳腺癌患者Th细胞呈现Th1抑制和Th2极化状态，细胞免疫受抑制。②手术切除肿瘤可在早期一定程度上逆转Th1/Th2的失衡状态，改善机体免疫状态，对预后产生积极作用。
【Abstract】　Objective　 To investigate the expression and significance of helper T lymphocyte(Th) 1 and 2 of breast cancer patients in vivo before and after operation.　Methods　 From November 2009 to December 2010, Thl-type cytokines [interleukin-2 (IL-2), interferon-γ (IFN-γ)] and Th2-type cytokines (IL-4, IL-6) expression in supernatants of peripheral blood mononuclear cells (PBMC) were detected by enzyme-linked immunosorbent assay (ELISA) in 40 breast cancer patients before and after surgery (Breast cancer group) and 15 healthy women (Control group).　Results　 The test results of IL-2, IFN-γ, IL-4 and IL-6 in peripheral blood for patients of breast cancer group were (326.5±67.4), (288.5±35.6), (41.2±10.8), and (526.1±136.4) ng/L before surgery, and (958.1±284.7), (559.6±106.9), (26.1±8.7), and (395.6±125.9) ng/L after surgery. Those results for patients in the normal control group were (1498.0±325.9), (784.6±126.3), (16.6±3.7), and (297.4±83.7) ng/L respectively. Compared with the control group, the expression of peripheral blood Th1-type cytokines in pre-operative breast cancer patients was significantly lower, while expression of Th2-type cytokines was significantly higher (P lt;0.05); Compared with the pre-operative data, the expression of peripheral blood Th1-type cytokines in post-operative breast cancer patients was significantly higher, and the expression of Th2-type cytokines was significantly lower (P lt;0.05).　Conclusions　 ①For Th cells in breast cancer patients, there is a tendency of Th1 suppression and Th2 polarization, and cellular immunity is suppressed. ②To some extent, surgical removal of tumors can reverse the Th1/Th2 imbalance early, improve the immune status, and has a positive effect on the prognosis.

Citation： YUE Yanhong,SUN Zhijun. The Expression and Significance of Helper T Lymphocyte 1 and 2 Type Cytokines before and after Breast Cancer Surgery. West China Medical Journal, 2011, 26(7): 979-982. doi: Copy

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3.	Schreck S, Friebel D, Buettner M, et al. Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical hodgkin lymphoma[J]. Hematol Oncol, 2009, 27(1): 31-39.
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5.	Asselin-paturel C, Echchakir H, Carayol G, et al. Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, til and PBL of non-small cell lung cancer patients[J]. Int J Cancer, 1998, 77(1): 7-12.
6.	Greene FL, Compton CC, Fritz AG. AJCC cancer staging atlas[M]. 6th ed. New York: Springer Science-Business Media, inc., 2006: 217-235.
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8.	乔治, 李荣, 徐迎新, 等. Th1/Th2及Tc1/Tc2在胃癌患者外周血中的漂移及意义[J]. 世界华人消化杂志, 2009, 17(12): 1238-1240.
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10.	Aoki Y, Tsuneki I, Sasaki M, et al. Analysis of TH1 and TH2 cells by intracellular cytokine detection with flow cytometry in patients with ovarian cancer[J]. Gynecol Obstet Invest, 2000, 50(3): 207-211.
11.	沈洪彦, 孙治君. Thl/Th2细胞与肿瘤复发[J]. 中国普外基础与临床杂志, 2006, 13(4): 490-492.
12.	Yamazaki K, Yano T, Kameyama T, et al. Clinical significance of serum TH1/TH2 cytokines in patients with pulmonary adenocarcinoma[J]. Surgery, 2002, 131(Suppl 1): 236-241.
13.	Denardo DG, Andreu P, Coussens LM. Interactions between lymphocytes and myeloid cells regulate pro-versus anti-tumor immunity[J]. Cancer Metastasis Rev, 2010, 29(2): 309-316.
14.	安云庆, 高晓明. 医学免疫学[M]. 北京: 北京大学医学出版社, 2004: 74-78.
15.	陈建国, 项永兵, 陈可欣. 启东、上海、天津恶性肿瘤发病率趋势比较研究[J]. 中国肿瘤, 2006, 15(10): 640-645.
16.	Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer[J]. Breast Cancer Res, 2002, 4(2): 65-69.
17.	Shurin MR, Lu L, Kalinski P, et al. Th1/Th2 balance in cancer, transplantation and pregnancy[J]. Springer Semin Immunopathol, 1999, 21(3): 339-359.
18.	Ehi K, Ishigami S, Masamoto I, et al. Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer[J]. Oncol Rep, 2008, 19(3): 601-607.
19.	沈洪彦, 孙治君, 于冰. Thl/Th2在乳腺癌组织中的表达与意义[J]. 第四军医大学学报, 2007, 28(20): 1899-1901.
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1. 　Romagnani S. Human TH1 and TH2 subsets: doubt no more[J]. Immunol Today, 1991, 12(8): 256-257.
2. 　Chechlińska M, Duma A, Swierkowska K, et al. Sera of lung cancer patients affect the release of Th1, Th2 and monocyte-derived cytokines, and the expression of IL-2R alpha by normal, stimulated mononuclear cells[J]. Cell Mol Biol Lett, 2004, 9(1): 69-81.
3. 　Schreck S, Friebel D, Buettner M, et al. Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical hodgkin lymphoma[J]. Hematol Oncol, 2009, 27(1): 31-39.
4. 　Yang P, Qiu G, Wang S, et al. The mutations of Th1 cell-specific T-box transcription factor may be associated with a predominant Th2 phenotype in gastric cancers[J]. Int J Immunogenet, 2010, 37(2): 111-115.
5. 　Asselin-paturel C, Echchakir H, Carayol G, et al. Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, til and PBL of non-small cell lung cancer patients[J]. Int J Cancer, 1998, 77(1): 7-12.
6. 　Greene FL, Compton CC, Fritz AG. AJCC cancer staging atlas[M]. 6th ed. New York: Springer Science-Business Media, inc., 2006: 217-235.
7. 　张圣林, 邱法波, 吴力群. Th1/Th2偏移与恶性肿瘤关系的研究进展[J]. 细胞与分子免疫学杂志, 2005, 21(Suppl): 113-114.
8. 　乔治, 李荣, 徐迎新, 等. Th1/Th2及Tc1/Tc2在胃癌患者外周血中的漂移及意义[J]. 世界华人消化杂志, 2009, 17(12): 1238-1240.
9. 　Matar P, Rozados VR, Gervasoni SI, et al. Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model[J]. Cancer Immunol Immunother, 2002, 50(11): 588-596.
10. 　Aoki Y, Tsuneki I, Sasaki M, et al. Analysis of TH1 and TH2 cells by intracellular cytokine detection with flow cytometry in patients with ovarian cancer[J]. Gynecol Obstet Invest, 2000, 50(3): 207-211.
11. 　沈洪彦, 孙治君. Thl/Th2细胞与肿瘤复发[J]. 中国普外基础与临床杂志, 2006, 13(4): 490-492.
12. 　Yamazaki K, Yano T, Kameyama T, et al. Clinical significance of serum TH1/TH2 cytokines in patients with pulmonary adenocarcinoma[J]. Surgery, 2002, 131(Suppl 1): 236-241.
13. 　Denardo DG, Andreu P, Coussens LM. Interactions between lymphocytes and myeloid cells regulate pro-versus anti-tumor immunity[J]. Cancer Metastasis Rev, 2010, 29(2): 309-316.
14. 　安云庆, 高晓明. 医学免疫学[M]. 北京: 北京大学医学出版社, 2004: 74-78.
15. 　陈建国, 项永兵, 陈可欣. 启东、上海、天津恶性肿瘤发病率趋势比较研究[J]. 中国肿瘤, 2006, 15(10): 640-645.
16. 　Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer[J]. Breast Cancer Res, 2002, 4(2): 65-69.
17. 　Shurin MR, Lu L, Kalinski P, et al. Th1/Th2 balance in cancer, transplantation and pregnancy[J]. Springer Semin Immunopathol, 1999, 21(3): 339-359.
18. 　Ehi K, Ishigami S, Masamoto I, et al. Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer[J]. Oncol Rep, 2008, 19(3): 601-607.
19. 　沈洪彦, 孙治君, 于冰. Thl/Th2在乳腺癌组织中的表达与意义[J]. 第四军医大学学报, 2007, 28(20): 1899-1901.
20. 　Romani L, Mencacci A, Tonnetti L, et al. IL-12 is both required and prognostic in vivo for T helper type 1 differentiation in murine candidiasis[J]. J Immunol, 1994, 153(11): 5167-5175.

West China Medical Journal

The Expression and Significance of Helper T Lymphocyte 1 and 2 Type Cytokines before and after Breast Cancer Surgery

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