In this issue of Blood, Goodyear and colleagues show that CD8 T-cell immunity against melanoma-associated antigen (MAGE)—a cancer testis antigen (CTA) not normally expressed in hematopoietic cells—is induced in leukemia patients treated with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors azacitidine (AZA) and sodium valproate (VPA), respectively. The authors report that up-regulation of MAGE in acute myeloid leukemia (AML) by AZA plus VPA is associated with major clinical responses and an increase of MAGE-specific effector T cells. Will this observation lead to testing of these drugs in immune-therapy strategies?