The transcription factor signal transducer and activator of transcription 3 (STAT3) is perhaps best known for its prosurvival effects in a wide variety of cancers, but for some, including acute myeloid leukemia (AML), its role in immune evasion may be just as important. In this issue of Blood, Zhang et al report the development of an engineered STAT3 decoy oligodeoxynucleotide (dODN) that is stable in serum, is taken up specifically by target cells, and exerts its antileukemia effects largely by restoring the host anti-AML immune response.