Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach.

British Journal of Cancer
M YoshiiK Hirakawa

Abstract

It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma. We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines. Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-β augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown. Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune...Continue Reading

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Citations

Jul 27, 2014·Cancer Immunology, Immunotherapy : CII·Christel DevaudMichael H Kershaw
Mar 14, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Leiguang YeBaogang Liu
Aug 25, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Srikanth SanthanamMatthew A Ciorba
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Methods Mentioned

BETA
density gradient centrifugation
electrophoresis
FCS

Software Mentioned

SPSS

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