Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse.
Valentina GambacortaStefano BerettaMartina CiccimarraLaura ZitoKety GiannettiAngela AndrisaniDaniela GnaniLucia ZanottiGiacomo OliveiraMatteo Giovanni Giovanni CarrabbaDavide CittaroIvan MerelliFabio CiceriRaffaella Di MiccoLuca VagoPublished in: Cancer discovery (2022)
Loss of HLA class II expression represents a frequent mechanism of leukemia posttransplantation relapse. Here we identify PRC2 as the main epigenetic driver of this immune escape modality and show that its chemical inhibition can reinstate a proficient graft-versus-leukemia effect, providing an innovative rationale for personalized epigenetic immunotherapies. See related commentary by Köhler and Zeiser, p. 1410. This article is highlighted in the In This Issue feature, p. 1397.