胃癌患者手術前后CD4+CD25+調節性T細胞的變化_《中國普外基礎與臨床雜志》

作者：

史學菲 , 白平 , 唐承薇 , 王春暉

四川大學華西醫院消化內科（四川成都 610041）;

關鍵詞：

調節性T細胞 FoxP3基因胃癌

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目的研究胃癌患者手術前、后調節性T細胞(Treg)及FoxP3表達的變化。方法采用流式細胞術檢測20例胃癌患者術前及其中15例接受了手術者術后1周（簡稱術后）以及15例因胃部不適接受胃鏡檢查的自愿者（正常對照組）外周血中Treg數量的變化，用RTPCR法檢測Treg的特異性分子標志物FoxP3的轉錄水平，同時用免疫組織化學法檢測胃癌組織中FoxP3蛋白的表達情況。結果胃癌患者術前外周血中CD4+T細胞中的CD4+CD25+比例明顯高于正常對照組〔(19.39±5.58)%比(9.91±3.23)%, P lt;0.01〕，而術后CD4+CD25+比例較術前明顯下降〔(13.50±5.93)%比(19.39±5.58)%，P lt;0.05〕。胃癌患者術前外周血中FoxP3轉錄水平明顯高于正常對照組(0.86±0.03比0.64±0.02，P lt;0.01)，而術后較術前明顯下降(0.73±0.04 比0.86±0.03,P lt;0.05)，提示FoxP3轉錄水平與Treg變化一致。胃癌患者外周血中CD4+T細胞在單個核細胞中的比例與正常對照組相比明顯下降(P lt;0.01)，而手術前、后變化不明顯。20例胃癌患者中13例胃癌癌細胞的細胞漿中有不同程度的FoxP3蛋白表達（強陽性2例，中陽性6例，弱陽性5例），7例胃癌患者的胃癌細胞中不表達。結論Treg可能通過免疫抑制作用在胃癌的發生、發展中發揮作用，腫瘤組織本身可能是引起Treg變化的重要始動因素。

引用本文： 史學菲,白平,唐承薇,王春暉. 胃癌患者手術前后CD4+CD25+調節性T細胞的變化. 中國普外基礎與臨床雜志, 2011, 18(9): 942-946. doi: 復制

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11.	Schuler PJ, Brger V, Blke E, et al. Dendritic cell generation and CD4+ CD25high FOXP3+ regulatory T cells in human head and neck carcinoma during radiochemotherapy [J]. Eur J Med Res, 2011, 16(2): 5762.
12.	Eikawa S, Ohue Y, Kitaoka K, et al. Enrichment of Foxp3+ CD4 regulatory T cells in migrated T cells to IL6 and IL8expressing tumors through predominant induction of CXCR1 by IL6 [J]. J Immunol, 2010, 185(11): 67346740.
13.	Petrausch U, Jensen SM, Twitty C, et al. Disruption of TGFbeta signaling prevents the generation of tumorsensitized regulatory T cells and facilitates therapeutic antitumor immunity [J]. J Immunol, 2009, 183(6): 36823689.
14.	林琳, 梁健, 馬作紅, 等. 胰十二指腸切除術對胰頭癌患者CD4+CD25+調節性T細胞的影響及臨床意義 [J]. 中國普外基礎與臨床雜志, 2011, 18(1): 5154.
15.	傅冷西, 張聲, 陳思曾. T細胞共刺激分子及其亞群在胃癌和大腸癌組織中表達的意義 [J]. 中國普外基礎與臨床雜志, 2008, 15(1): 5155.
16.	Bjoern J, Brimnes MK, Andersen MH, et al. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and lowdose IL2 [J]. Scand J Immunol, 2011, 73(3): 222233.
17.	Cao D, Malmstrm V, BaecherAllan C, et al. Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis [J]. Eur J Immunol, 2003, 33(1): 215223.
18.	Salama P, Phillips M, Grieu F, et al. Tumorinfiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer [J]. J Clin Oncol, 2009, 27(2): 186192.
19.	Liotta F, Gacci M, Frosali F, et al. Frequency of regulatory T cells in peripheral blood and in tumourinfiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma [J]. BJU Int, 2011, 107(9): 15001506.
20.	Watanabe Y, Katou F, Ohtani H, et al. Tumorinfiltrating lymphocytes, particularly the balance between CD8+ T cells and CCR4+ regulatory T cells, affect the survival of patients with oral squamous cell carcinoma [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010, 109(5): 744752.
21.	Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3 [J]. Science, 2003, 299(5609): 1057106.
22.	Lal G, Bromberg JS. Epigenetic mechanisms of regulation of Foxp3 expression [J]. Blood, 2009, 114(18): 37273735.

1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J]. Int J Cancer, 2010, 127(12): 28932917.
2. Jemal A, Bray F, Center MM, et al. Global Cancer Statistics [J]. CA Cancer J Clin, 2011, 61(2): 6990.
3. Sasako M, Inoue M, Lin JT, et al. Gastric cancer working group report [J]. Jpn J Clin Oncol, 2010, 40 Suppl 1: i28i37.
4. Casares N, Arribillaga L, Sarobe P, et al. CD4+CD25+ regulatory cells inhibit activation of tumorprimed CD4+T cells with IFNgammadependent antiangiogenic activity, as well as longlasting tumor immunity elicited by peptide vaccination [J]. J Immunol, 2003, 171(11): 59315939.
5. Sutmuller RP, van Duivenvoorde LM, van Elsas A, et al. Synergism of cytotoxic T lymphocyteassociated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses [J]. J Exp Med, 2001, 194(6): 823832.
6. Antony PA, Restifo NP. CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin2 [J]. J Immunother, 2005, 28(2): 120128.
7. Hinz S, PagerolsRaluy L, Oberg H, et al. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer [J]. Cancer Research, 2007, 67(17): 83448350.
8. Corthay A. How do regulatory T cells work? [J]. Scand J Immunol, 2009, 70(4): 326336.
9. Jiang S, Lechler RI. CD4+CD25+ regulatory Tcell therapy for allergy, autoimmune disease and transplant rejection [J]. Inflamm Allergy Drug Targets. 2006, 5(4): 239242.
10. BaecherAllan C, Brown JA, Freeman GJ, et al. CD4+CD25high regulatory cells in human peripheral blood [J]. J Immunol, 2001, 167(3): 12451253.
11. Schuler PJ, Brger V, Blke E, et al. Dendritic cell generation and CD4+ CD25high FOXP3+ regulatory T cells in human head and neck carcinoma during radiochemotherapy [J]. Eur J Med Res, 2011, 16(2): 5762.
12. Eikawa S, Ohue Y, Kitaoka K, et al. Enrichment of Foxp3+ CD4 regulatory T cells in migrated T cells to IL6 and IL8expressing tumors through predominant induction of CXCR1 by IL6 [J]. J Immunol, 2010, 185(11): 67346740.
13. Petrausch U, Jensen SM, Twitty C, et al. Disruption of TGFbeta signaling prevents the generation of tumorsensitized regulatory T cells and facilitates therapeutic antitumor immunity [J]. J Immunol, 2009, 183(6): 36823689.
14. 林琳, 梁健, 馬作紅, 等. 胰十二指腸切除術對胰頭癌患者CD4+CD25+調節性T細胞的影響及臨床意義 [J]. 中國普外基礎與臨床雜志, 2011, 18(1): 5154.
15. 傅冷西, 張聲, 陳思曾. T細胞共刺激分子及其亞群在胃癌和大腸癌組織中表達的意義 [J]. 中國普外基礎與臨床雜志, 2008, 15(1): 5155.
16. Bjoern J, Brimnes MK, Andersen MH, et al. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and lowdose IL2 [J]. Scand J Immunol, 2011, 73(3): 222233.
17. Cao D, Malmstrm V, BaecherAllan C, et al. Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis [J]. Eur J Immunol, 2003, 33(1): 215223.
18. Salama P, Phillips M, Grieu F, et al. Tumorinfiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer [J]. J Clin Oncol, 2009, 27(2): 186192.
19. Liotta F, Gacci M, Frosali F, et al. Frequency of regulatory T cells in peripheral blood and in tumourinfiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma [J]. BJU Int, 2011, 107(9): 15001506.
20. Watanabe Y, Katou F, Ohtani H, et al. Tumorinfiltrating lymphocytes, particularly the balance between CD8+ T cells and CCR4+ regulatory T cells, affect the survival of patients with oral squamous cell carcinoma [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010, 109(5): 744752.
21. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3 [J]. Science, 2003, 299(5609): 1057106.
22. Lal G, Bromberg JS. Epigenetic mechanisms of regulation of Foxp3 expression [J]. Blood, 2009, 114(18): 37273735.

《中國普外基礎與臨床雜志》

胃癌患者手術前后CD4+CD25+調節性T細胞的變化

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《中國普外基礎與臨床雜志》

胃癌患者手術前后CD4+CD25+調節性T細胞的變化

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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