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Targeting EZH2 depletes LMP1-induced activated regulatory T cells enhancing antitumor immunity in nasopharyngeal carcinoma.
- Source :
-
Journal of Cancer Research & Therapeutics . Apr-Jun2020, Vol. 16 Issue 2, p309-319. 11p. - Publication Year :
- 2020
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SUPPRESSOR cells
*IMMUNITY
*T cells
*MEMBRANE proteins
*CARCINOMA
*T cell receptors
Subjects
Details
- Language :
- English
- ISSN :
- 09731482
- Volume :
- 16
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 143504507
- Full Text :
- https://doi.org/10.4103/jcrt.JCRT_986_19