Influence of Pancreatoduodenectomy on CD4+CD25+ T Cells in Patients with Pancreatic Head Carcinoma and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIN Lin ¹ , LIANG Jian ¹ , MA Zuohong ² , GUO Dawei ¹ , WANG Xuefan ¹ , FU Qingcai ² , SUN Wenyu ¹ , JIANG Honglei ¹ , JIN Junzhe ¹ ,  JIANG Xiaofeng ¹

1.Department of Hepatiobiliaripancreatic Surgery， The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China;;
2.Department of Hepatiobiliaripancreatic Surgery, Cancer Hospital of Liaoning Province, Shenyang 110043, Liaoning Province, China;

Corresponding author：

JIANG Xiaofeng, Email: jiang_xiaofeng@hotmail.com

Keywords：

Carcinoma of pancreatic head; Pancreatoduodenectomy; Regulatory T cells; Immunotolerance

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ObjectiveTo investigate the proportion of peripheral blood CD4+CD25+ regulatory T cells (Tregs) in patients with pancreatic head carcinoma, the dynamic changes of these cells before and after pancreatoduodenectomy were also analyzed. MethodsThe proportions of peripheral blood CD4+CD25+ Tregs in patients with pancreatic head carcinoma and normal individuals were examined by using flow cytometric analysis. The CD4+/CD8+ ratio was also studied before and after operation. ResultsThe patients with pancreatic head carcinoma showed higher ratio of CD4+CD25+ and CD4+CD25high Tregs compared with normal control before operation (P lt;0.05). However, the percentage of these T cells reduced significantly after pancreatoduodenectomy, which was most obviously on the 3rd day after operation (P lt;0.01, P lt;0.05). After operation, CA199 level began to decrease, which was obvious on the fourteen day after operation. This tendency of CD4+CD25high Tregs changes was similar to that of CA199. The patients showed an decreased ratios of CD4+/CD8+ compared with normal controls, which further declined after operation, and reached the lowest point on the seventh day after operation (P lt;0.05). ConclusionsPancreatoduodenectomy may be helpful for the recovery of antitumor immunity. The perioperative period of patients with pancreatic head carcinoma may be a beneficial windowphase for immune intervention and Tregs may be served as target cells.

Citation： LIN Lin ,LIANG Jian,MA Zuohong,GUO Dawei,WANG Xuefan,FU Qingcai,SUN Wenyu,JIANG Honglei,JIN Junzhe,JIANG Xiaofeng. Influence of Pancreatoduodenectomy on CD4+CD25+ T Cells in Patients with Pancreatic Head Carcinoma and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(1): 51-54. doi: Copy

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.	刘俊田，岳杰，任秀宝，等. 乳腺癌患者外周血CD4+CD25+调节性T细胞的检测及意义 [J]. 中华肿瘤杂志， 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.	邬玉辉，申正堂，海健，等. 乳腺癌患者细胞免疫功能的检测 [J]. 中国医师杂志， 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. 刘俊田，岳杰，任秀宝，等. 乳腺癌患者外周血CD4+CD25+调节性T细胞的检测及意义 [J]. 中华肿瘤杂志， 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. 邬玉辉，申正堂，海健，等. 乳腺癌患者细胞免疫功能的检测 [J]. 中国医师杂志， 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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