PRC2 Epigenetically Silences XXXX -Type Chemokines to Suppress Effector T-Cell Trafficking in @entity694 .

@entity1 @entity404 @entity38612 @entity5 @entity16719 @entity694 @entity1198 @entity376 @entity373 @entity371 @entity45938 @entity405
UNASSIGNED: Infiltration of @entity5 with effector T cells is positively associated with therapeutic efficacy and @entity1 survival. However, the mechanisms underlying effector T-cell trafficking to the @entity5 microenvironment remain poorly understood in @entity1 with @entity694 . The polycomb repressive complex 2 (PRC2) is involved in @entity5 progression, but the regulation of @entity5 immunity by epigenetic mechanisms has yet to be investigated. In this study, we examined the relationship between the repressive PRC2 machinery and effector T-cell trafficking. We found that PRC2 components and demethylase @entity45938 -mediated histone H3 @entity376 27 trimethylation (H3K27me3) repress the expression and subsequent production of @entity1198 -type chemokines @entity373 and @entity371 , mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including @entity16719 , @entity38612 , and EED, were inversely associated with those of @entity404 , @entity405 , and @entity1198 -type chemokines in @entity1 @entity694 tissue, and this expression pattern was significantly associated with @entity1 survival. Collectively, our findings reveal that PRC2-mediated epigenetic silencing is not only a crucial oncogenic mechanism, but also a key circuit controlling @entity5 immunosuppression. Therefore, targeting epigenetic programs may have significant implications for improving the efficacy of current @entity5 immunotherapies relying on effective T-cell-mediated immunity at the @entity5 site. @entity5 Res; 76(2); 275-82.   2015 AACR.
