Change of CD4+CD25+ Regulatory T Cells in Patients with Gastric Cancer before and after Operation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHI Xuefei , BAI Ping , TANG Chengwei , WANG Chunhui.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

Keywords：

Regulatory T cell; FoxP3 gene; Gastric cancer

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

ObjectiveTo investigate the levels of regulatory T cells (Treg) and FoxP3 gene in patients with gastric cancer before and after operation. MethodsTwenty patients with definite diagnosis of gastric cancer and 15 healthy volunteers were selected. The levels of Treg and T cell subsets in peripheral blood were determined by detecting of CD4 and CD25 with immunefluorescence stain and flow cytometry, the expressions of FoxP3 mRNA in these Treg were detected by RTPCR technique. The expression of FoxP3 protein in the gastric cancer tissue was measured by immunohistochemistry assay. ResultsThe percentage of Treg cells in total CD4+ T isolated from the patients with gastric cancer was higher than that of healthy volunteers 〔(19.39±5.58)% versus (9.91±3.23)%, P lt;0.01〕, and it markedly decreased after operation 〔（13.50±5.93）% versus (19.39±5.58)%, P lt;0.05〕. The FoxP3 mRNA expression in the patients with gastric cancer was also higher than that of healthy volunteers (0.86±0.03 versus 0.64±0.02, P lt;0.01), and decreased after operation (0.73±0.04 versus 0.86±0.03, P lt;0.05). The percentage of CD4+T cell in mononucleocytes of peripheral blood of patients with gastric cancer was significantly lower than that of healthy volunteers (P lt;0.01), but the difference was not significant between before and after operation. FoxP3 protein expressed in cytoplasm of 13 patients with gastric cancer, in which bly positive in 2 cases, middle positive in 6 cases, weakly positive in 5 cases. FoxP3 protein didn’t express in cytoplasm of 7 patients with gastric cancer. ConclusionsTreg may have a significant effect on the onset and development of gastric cancer through immunosuppressive effect. Tumor tissue is an important initiating agent on Treg proliferation.

Citation： SHI Xuefei,BAI Ping,TANG Chengwei,WANG Chunhui.. Change of CD4+CD25+ Regulatory T Cells in Patients with Gastric Cancer before and after Operation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(9): 942-946. doi: Copy

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, 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.
15.	傅冷西, 张声, 陈思曾. T细胞共刺激分子及其亚群在胃癌和大肠癌组织中表达的意义 [J]. 中国普外基础与临床杂志, 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, 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.
15. 傅冷西, 张声, 陈思曾. T细胞共刺激分子及其亚群在胃癌和大肠癌组织中表达的意义 [J]. 中国普外基础与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Change of CD4+CD25+ Regulatory T Cells in Patients with Gastric Cancer before and after Operation

Abstract Full text Figures/Tables Video References Cited by

Format

Content