Mechanisms of Epstein-Barr virus nuclear antigen 1 favor Tregs accumulation in nasopharyngeal carcinoma.

ABSTRACT

BACKGROUND: Documented reports proved that Epstein-Barr virus (EBV) infection increased infiltration of Tregs in malignancy. However, the mechanism of EBV recruitment Tregs into nasopharyngeal carcinoma (NPC) tissues has not been detailed discussion. METHODS: Expression of EBV nuclear antigen 1 (EBNA1) and Foxp3 in NPC tissue samples was detected by immunohistochemistry. EBNA1+ NPC cell lines were used to coculture with PBMC, naïve T cells, Tregs, and monocytes. Percent of Treg was detected by flow cytometry. RESULTS: EBNA1 protein was overexpressed in NPC tissues, and was associated with a number of infiltrated Tregs. EBNA1+ NPC cells converted naïve T cells into Tregs by up-regulated TGF-ß1. Enhanced CCL20 production in EBNA1-expressed tumor cells increased Tregs migration. Polarized-M2 macrophages by EBNA1 expression cells converted naïve T cells into Tregs. CONCLUSIONS: EBNA1 favors accumulation of Tregs in NPC through (a) upregulated TGF-ß1 converted naïve T cell into Treg; (b) upregulated CCL20 increased Treg migration; and (c) polarized-M2 macrophage converted naïve T cell into Treg.