BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML[RNA]

We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. our findings reveal a previously unidentified mechanism of NK immune evasion in AML manifested by epigenetic rewiring and inactivation of NK cells by myeloid blasts.? This work highlights the importance of using healthy allogeneic NK cells as adoptive cell therapy to treat patients with myeloid malignancies combined with strategies aimed at preventing the dysfunction by targeting the TGF-b pathway or BATF Overall design: Libraries were sequenced Illumina NovaSeq6000. Samples: 1-NKcellsfromPB1withCas9only 2-NKcellsfromPB2withCas9only 3-NKcellsknockoutforTGFbR2fromPB1 4-NKcellsknockoutforTGFbR2fromPB2 5-NKcellsfromPB1withCas9only cocultured directly with AML1cells 6-NKcellsfromPB2withCas9only cocultured directly with AML1cells 7- NKcellsfromPB2withCas9only cocultured directly with AML2cells 8-NKcellsfromPB1withCas9only cocultured through transwell with AML1cells 9-NKcellsfromPB2withCas9only cocultured through transwell with AML1cells 10-NKcellsfromPB1withCas9only cocultured through transwell with AML2cells 11-NKcellsknockoutforTGFbR2fromPB1 cocultured directly with AML1cells 12-NKcellsknockoutforTGFbR2fromPB2 cocultured directly with AML1cells 13-NKcellsknockoutforTGFbR2fromPB1 cocultured directly with AML2cells 14-NKcellsknockoutforTGFbR2fromPB1 cocultured directly with AML2cells