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Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor-β1

✍ Scribed by Xiaoming Lu; Jun Liu; Hang Li; Wei Li; Xuesong Wang; Jingwei Ma; Qiang Tong; Ke Wu; Guobin Wang


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
314 KB
Volume
104
Category
Article
ISSN
0022-4790

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✦ Synopsis


Abstract

Background and Objectives

Regulatory T cells (Treg) inhibits immune responses mediated by T cells. This study aimed to investigate whether Treg are accumulated in human gastric cancer tissue and the mechanism of Treg induction by gastric cancer cells.

Methods

Tissue infiltrated leukocytes from gastric adenocarcinomas were subjected to flow cytometry and immunohistochemistry. Percentage, phenotype, function, and clinical relevance of Treg were analyzed. TGF‐β1 production by cancer cells was determined by Western blot and in vitro co‐culture experiments were performed to mimic gastric cancer microenvironment.

Results

The percentages of CD4^+^Foxp3^+^ T cells in gastric cancer tissues were significantly higher than those from adjacent non‐tumor gastric tissues (P < 0.05). The results of classical Treg phenotype and proliferation assay supported that the elevated CD4^+^Foxp3^+^ T cells represents a suppressive Treg population. High proportion of Treg is correlated to advance TNM stage and reduced survival. Primary gastric cancer cells produced abundance of TGF‐β1 which was responsible for conversion of Treg.

Conclusion

The proportion of functional Treg is elevated in human gastric cancer and related to poor prognosis. Gastric cancer cells directly convert CD4^+^ naive T cells to Treg by TGF‐β1, suggesting a possible mechanism through which tumor cells evade the immune system. J. Surg. Oncol. 2011; 104:571–577. © 2011 Wiley Periodicals, Inc.


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