Tumor-infiltrating Foxp3+ Regulatory T Cells Contribute to Partial EMT through the Snail+ Tumor Cell Feedback Loop in Nasopharyngeal Carcinoma Patients
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Abstract
Tumor-infiltrating FoxP3+ Treg cells are crucial immune components associated with progressivity, metastasis, and prognosis in various malignancies, but the role in nasopharyngeal carcinoma (NPC) is not fully understood. Therefore, this study aimed to investigate the role of infiltrating FoxP3+ Treg cells in epithelial-mesenchymal transition (EMT) in NPC patients. A total of 57 paraffin blocks from NPC patients were included in this study. The samples were then deparaffinized, and double immunohistochemical staining was performed to examine infiltrating Tregs that colocalize to express FoxP3+ and TGF-β1. Single immunohistochemical staining was conducted to examine NPC tumor cells that express EMT markers Snail, E-cadherin, and vimentin. Chi-square and the Gamma correlation tests were used, with a P-value <0.05 considered statistically significant. The results showed that most NPC samples had low expression of Foxp3+ Treg cells (59.6%), TGF-β1 (63.2%), E-cadherin (87.7%), and vimentin (75.4%), while Snail expression was high (66.7%). There was no relationship between the expression of Foxp3+ Treg and pathologic variables except with Snail (P = 0.001; Gamma correlation test, r = 0.826, P < 0.001). TGF-β1 expression showed no association with Snail. Meanwhile, Snail was significantly associated with vimentin (P = 0.022; Gamma correlation test, r = 0.807, P = 0.003) but not with E-cadherin. Snail was also significantly associated with Foxp3+ Treg expression (P = 0.003; Gamma correlation test, r = 0.826, P < 0.001). These results suggest that infiltrating Foxp3+ Treg cells contribute to partial EMT in NPC with immunosuppressive function by forming a feedback loop with Snail+ tumor cells.
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