EZH2 inhibits NK cell–mediated antitumor immunity by suppressing CXCL10 expression in an HDAC10-dependent manner
Suresh Bugide, Romi Gupta, Michael R. Green, Narendra Wajapeyee
Abstract
transcriptional repression. Critically, CXCL10 is necessary and sufficient for stimulating NK cell migration, and EZH2's ability to inhibit NK cell migration via CXCL10 suppression is conserved in other EZH2-dependent cancers. NK cell depletion in an immunocompetent syngeneic mouse model of hepatic tumorigenesis reverses the tumor inhibitory effects of an EZH2 inhibitor (GSK343), and inhibitor-mediated reexpression of CXCL10 is required for its tumor suppressive effects in the same mouse model. Collectively, these results reveal a decisive role for NK cells and CXCL10 in mediating the oncogenic function of EZH2.
Topics & Concepts
EZH2ImmunityCancer researchCXCL10Expression (computer science)Cell mediated immunityCell biologyImmunologyMedicineBiologyImmune systemGene expressionChemokineGeneComputer scienceGeneticsProgramming languageImmune Cell Function and InteractionEpigenetics and DNA MethylationHistone Deacetylase Inhibitors Research