首页|B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

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AIM:To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment.METHODS:One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study.Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues.Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells.Data was analyzed with statistical software.RESULTS:Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues,localized in tumor cell membrane and cytoplasm,while weak or none expression of B7-H1 was detected in pared normal colorectal tissues.Meanwhile,CD3 positive T cells were found congregated in CRC tumor nest and stroma.Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P ＜ 0.0001) and tumor stroma (P =0.0200) of 102 cases of CRC tissues.Among the total T cells,a variable amount of regulatory T cells with a clear Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients' blood.Interestingly,in the 33 samples (15 cases of B7-High CRC tissues and 18 cases of B7-H1low CRC tissues) of freshly isolated mononuclear cells from CRC tissues,the percentages of CD4+Foxp3+ and CD8+Foxp3+ regulatory T cells were found remarkably higher in B7-H1high CRC tissues than in B7-H1ow CRC tissues (P =0.0024,P =0.0182),indicating that B7-H1 expression was involved in proliferation of regulatory T cell.No significant difference was found in CRC peripheral blood (P =0.0863,P =0.0678).PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell,which is expressed by activated T cell.Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4+Foxp37 CD8+Foxp3-),which was thought to contribute to the anti-tumor immune response,highly expressed PD-1;while regulatory T cells (CD4+Foxp3+/CD8+Foxp3) almost failed to express PD-1.The average percentage of PD-1 expression on regulatory T cells was significantly higher than the percentage of PD-1 on conventional T cells (CD4+Foxp3 T cell,P ＜ 0.0001; CD8+Foxp3 T cell,P ＜ 0.0001).The diverse expression of PD-1 might lead to different fate of T cell subsets in B7-H1 over-expression CRC tumor microenvironment.CONCLUSION:B7-H1 expression in tumor cells can inhibit the conventional T cell proliferation in tumor microenvironment through the PD-1 expression on conventional T cells.

Costimulatory moleculeB7-H1PD-1Regulatory T cellColorectal carcinoma

Dong Hua、Jing Sun、Yong Mao、Lu-Jun Chen、Yu-Yu Wu、Xue-Guang Zhang

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Department of Oncology, the Fourth Affiliated Hospital of Suzhou University, Wuxi 214062, Jiangsu Province, China

Institute of Medical Biotechnology, Soochow University, Suzhou 215007, Jiangsu Province, China

Clinical central Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003, Jiangsu Province, China

Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, Jiangsu Province,China

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Grants from the Major State Basic Research Development Program of China 973 Program国家自然科学基金and "333" Project of Wuxi City,Jiangsu Province

2007CB512402BK2010161CAE00901-09

2012

10.3748/wjg.v18.i9.971

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(9)
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