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△_《中國普外基礎與臨床雜志》

作者：

林琳 ¹ , 梁健 ¹ , 馬作紅 ² , 郭大偉 ¹ , 王學范 ¹ , 付慶才 ² , 孫文郁 ¹ , 姜洪磊 ¹ , 金俊哲 ¹ ,  姜曉峰 ¹

1.中國醫科大學附屬第四醫院肝膽胰外科(遼寧沈陽 110032);;
2.遼寧省腫瘤醫院肝膽胰外科(遼寧沈陽 110043);

關鍵詞：

胰頭癌胰十二指腸切除術調節性T細胞免疫耐受

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目的研究胰頭癌患者外周血中CD4+CD25+調節性T細胞(Treg)比例及其在手術前、后的變化趨勢。方法采用流式細胞儀檢測胰頭癌患者及正常對照組外周血中CD4+CD25+調節性T細胞的數量，同時監測CD4+/CD8+比值，并進行手術前、后的比較。結果胰頭癌患者術前外周血中CD4+CD25+和CD4+CD25high Treg所占比例較正常對照組高(P lt;0.05)，術后則出現不同程度下降，以術后第3天下降最明顯(P lt;0.01，P lt;0.05)；胰頭癌患者術后CA199水平低于術前，以術后第14天下降明顯(P lt;0.05)。 CD4+CD25highTreg與CA199的變化趨勢大致相同。胰頭癌患者術前CD4+/CD8+比值比正常對照組低(P lt;0.05)，手術后進一步降低，于手術后第7天達最低(P lt;0.05)。結論胰十二指腸切除術可能有助于機體抗腫瘤免疫的恢復，胰頭癌患者圍手術期可作為免疫干預的重要窗口期，CD4+CD25+調節性T細胞可作為免疫干預的靶點。

引用本文： 林琳,梁健,馬作紅,郭大偉,王學范,付慶才,孫文郁,姜洪磊,金俊哲,姜曉峰. 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△. 中國普外基礎與臨床雜志, 2011, 18(1): 51-54. doi: 復制

1.	Michalski CW， Weitz J， Büchler MW. Surgery insight: surgical management of pancreatic cancer [J]. Nat Clin Pract Oncol, 2007, 4(9): 526535.
2.	Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic selftolenrance maintained by actived T cells expressing Il2 receptor αchain (CD25). Breakdown of a single mechanism of selftolerance causes various autoimmune disease [J]. J Immunol, 1995, 155(3): 11511164.
3.	Abdulamir AS， Kadhim HS， Hafidh RR， et al. Severity of asthma: the role of CD25+， CD30+， NFκB， and apoptotic markers [J]. J Investig Allergol Clin Immunol， 2009， 19(3): 218224.
4.	Stephens LA， Malpass KH， Anderton SM， et al. Curing CNS autoimmune disease with myelinreactive Foxp3+ Treg [J]. Eur J Immunol， 2009， 39(4): 11081117.
5.	Woo EY， Chu CS， Goletz TJ， et al. Regulatory CD4+CD25+ T cells in tumors from patients with earlystage nonsmall cell lung cancer and latestage ovarian cancer [J]. Cancer Res， 2001， 61(12): 47664772.
6.	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 dieases progression [J]. Cancer， 2003， 98(5): 10891099.
7.	Omandy LA， Hillemann T， Wedemeyer H， et al. Increased populations of regulatory T cells in peripheral blood of patients with hepatocelluar carcinoma [J]. Cancer Res， 2005， 65(6): 24572464.
8.	劉俊田，岳杰，任秀寶，等. 乳腺癌患者外周血CD4+CD25+調節性T細胞的檢測及意義 [J]. 中華腫瘤雜志， 2005， 27(7): 423425.
9.	Liyanage UK， Moore TT， Joo HG， et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma [J]. J Immunol， 2002， 169(5): 27562761.
10.	Hiraoka N， Onozato K， Kosuge T， et al. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions [J]. Clin Cancer Res， 2006， 12(18): 54235434.
11.	Kono K， Kawaida H， Takahashi A， et al. CD4+CD25high regulatory T cells increase with tumor stage in patient with gastric and esophageal cancers [J]. Cancer Immunol Immunother， 2006， 55(9): 10641071.
12.	Peng L， Kiaergard J， Plautz GE， et al. Tumorinduced Lselectin high suppressor T cells mediate potent effector T cell blockade and cause failure of otherwise curative adoptive immunotherapy [J]. J Immunol， 2002， 169(9): 48114821.
13.	鄔玉輝，申正堂，海健，等. 乳腺癌患者細胞免疫功能的檢測 [J]. 中國醫師雜志， 2001， 3(8): 627628.
14.	Sharma S， Yang SC， Zhu L， et al. Tumor cyclooxygenase2/prostaglandin E2dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in lung cancer [J]. Cancer Res， 2005， 65(12): 52115220.
15.	Valzasina B， Piconese S， Guiducci C， et al. Tumorinduced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent [J]. Cancer Res， 2006， 66(8): 44884495.
16.	Ghiringhelli F， Puig PE， Roux S， et al. Tumor cells conver immature myeloid dendritic cells into TGFβsecreting cells inducing CD4+CD25+ regulatory T cell proliferation [J]. J Exp Med， 2005， 202(7): 919929.
17.	MooYoung TA, Larson JW, Belt BA， et al. Tumorderived TGFβ mediates conversion of CD4+Foxp3+ regulatory T Cells in a murine model of pancreas cancer [J]. J Immunother, 2009, 32(1): 1221.
18.	Curiel J， Conkos G， Zou L， et al. Specifc recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J]. Nat Med， 2004，10(9): 942949.
19.	Dannull J， Su Z， Rizzieri D， et al. Enhancement of vaccinemediated antitumor immunity in cancer patients after depletion of regulatory T cells [J]. J Clin Invest， 2005， 115(12): 36233633.
20.	Nummer D, SuriPayer E, SchmitzWinnenthal H, et al. Role of tumor endothelium in CD4+CD25+ regulatory T cell infiltration of human pancreatic carcinoma [J]. J Natl Cancer Inst， 2007， 99(15): 11881199.

1. Michalski CW， Weitz J， Büchler MW. Surgery insight: surgical management of pancreatic cancer [J]. Nat Clin Pract Oncol, 2007, 4(9): 526535.
2. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic selftolenrance maintained by actived T cells expressing Il2 receptor αchain (CD25). Breakdown of a single mechanism of selftolerance causes various autoimmune disease [J]. J Immunol, 1995, 155(3): 11511164.
3. Abdulamir AS， Kadhim HS， Hafidh RR， et al. Severity of asthma: the role of CD25+， CD30+， NFκB， and apoptotic markers [J]. J Investig Allergol Clin Immunol， 2009， 19(3): 218224.
4. Stephens LA， Malpass KH， Anderton SM， et al. Curing CNS autoimmune disease with myelinreactive Foxp3+ Treg [J]. Eur J Immunol， 2009， 39(4): 11081117.
5. Woo EY， Chu CS， Goletz TJ， et al. Regulatory CD4+CD25+ T cells in tumors from patients with earlystage nonsmall cell lung cancer and latestage ovarian cancer [J]. Cancer Res， 2001， 61(12): 47664772.
6. 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 dieases progression [J]. Cancer， 2003， 98(5): 10891099.
7. Omandy LA， Hillemann T， Wedemeyer H， et al. Increased populations of regulatory T cells in peripheral blood of patients with hepatocelluar carcinoma [J]. Cancer Res， 2005， 65(6): 24572464.
8. 劉俊田，岳杰，任秀寶，等. 乳腺癌患者外周血CD4+CD25+調節性T細胞的檢測及意義 [J]. 中華腫瘤雜志， 2005， 27(7): 423425.
9. Liyanage UK， Moore TT， Joo HG， et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma [J]. J Immunol， 2002， 169(5): 27562761.
10. Hiraoka N， Onozato K， Kosuge T， et al. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions [J]. Clin Cancer Res， 2006， 12(18): 54235434.
11. Kono K， Kawaida H， Takahashi A， et al. CD4+CD25high regulatory T cells increase with tumor stage in patient with gastric and esophageal cancers [J]. Cancer Immunol Immunother， 2006， 55(9): 10641071.
12. Peng L， Kiaergard J， Plautz GE， et al. Tumorinduced Lselectin high suppressor T cells mediate potent effector T cell blockade and cause failure of otherwise curative adoptive immunotherapy [J]. J Immunol， 2002， 169(9): 48114821.
13. 鄔玉輝，申正堂，海健，等. 乳腺癌患者細胞免疫功能的檢測 [J]. 中國醫師雜志， 2001， 3(8): 627628.
14. Sharma S， Yang SC， Zhu L， et al. Tumor cyclooxygenase2/prostaglandin E2dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in lung cancer [J]. Cancer Res， 2005， 65(12): 52115220.
15. Valzasina B， Piconese S， Guiducci C， et al. Tumorinduced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent [J]. Cancer Res， 2006， 66(8): 44884495.
16. Ghiringhelli F， Puig PE， Roux S， et al. Tumor cells conver immature myeloid dendritic cells into TGFβsecreting cells inducing CD4+CD25+ regulatory T cell proliferation [J]. J Exp Med， 2005， 202(7): 919929.
17. MooYoung TA, Larson JW, Belt BA， et al. Tumorderived TGFβ mediates conversion of CD4+Foxp3+ regulatory T Cells in a murine model of pancreas cancer [J]. J Immunother, 2009, 32(1): 1221.
18. Curiel J， Conkos G， Zou L， et al. Specifc recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J]. Nat Med， 2004，10(9): 942949.
19. Dannull J， Su Z， Rizzieri D， et al. Enhancement of vaccinemediated antitumor immunity in cancer patients after depletion of regulatory T cells [J]. J Clin Invest， 2005， 115(12): 36233633.
20. Nummer D, SuriPayer E, SchmitzWinnenthal H, et al. Role of tumor endothelium in CD4+CD25+ regulatory T cell infiltration of human pancreatic carcinoma [J]. J Natl Cancer Inst， 2007， 99(15): 11881199.

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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△

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《中國普外基礎與臨床雜志》

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△

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