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- Title
Targeting EZH2 depletes LMP1-induced activated regulatory T cells enhancing antitumor immunity in nasopharyngeal carcinoma.
- Authors
Sun, Wei; Chen, Lin; Tang, Jun; Zhang, Chengcheng; Wen, Yihui; Wen, Weiping
- Abstract
<bold>Objective: </bold>Regulatory T cells (Tregs) are critical factors that impair antitumor immunity. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is one of the most pathogenic factors in nasopharyngeal carcinoma (NPC). However, the role of EBV-encoded LMP1 in regulating Treg generation in NPC remains unclear.<bold>Materials and Methods: </bold>The in vitro stability of activated Tregs (aTregs) influenced by LMP1 was analyzed by flow cytometry. The inhibitory effects of LMP1-HONE1 antigen-induced aTregs on tumor-associated antigen (TAA)-specific T cells were analyzed in vitro and in vivo. Finally, the expression of LMP1, Foxp3, and enhancer of zeste homolog 2 (EZH2) were analyzed in samples from 86 NPC patients by immunohistochemistry and immunofluorescence.<bold>Results: </bold>LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. EZH2 inhibitor, DZnep, depleted LMP1-HONE1 antigen-induced aTregs in vitro and led to potent TAA-specific T cell antitumor immunity in vivo. In NPC tissues, LMP1 expression level was positively correlated with the number of EZH2+ Tregs, which was positively correlated with clinical stage and overall survival.<bold>Conclusions: </bold>EZH2 is essential for maintaining the stability and inhibitory functions of aTregs that are induced by EBV-encoded LMP1 in NPC.
- Subjects
SUPPRESSOR cells; IMMUNITY; T cells; MEMBRANE proteins; CARCINOMA; T cell receptors
- Publication
Journal of Cancer Research & Therapeutics, 2020, Vol 16, Issue 2, p309
- ISSN
0973-1482
- Publication type
journal article
- DOI
10.4103/jcrt.JCRT_986_19