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Memory-like natural killer cell and CD19-antibody based immunotherapy in combination with tyrosine-kinase inhibition of Ph(-like) acute lymphoblastic leukemia (MethylationEPIC)

ABSTRACT: Epigenetic re-programming has been proposed to prime NK cells for an adaptive immune response. Additionally, priming NK cells with IL-12, IL-15, and IL-18 induces a memory-like condition marked by improved immune response capabilities when encountering target cells later on. In order to obtain a more thorough understanding of the memory-like state of NK cells induced by cytokines, we examined the impact of activating cytokines on the DNA methylation across the entire genome of NK cells derived from peripheral blood (referred to as PBNK cells). This investigation conducted after isolating the PBNK cells using antibody-bead isolation or after expanding them in a 7-day co-culture with irradiated K562 cells that expressed membrane-bound IL-21 and co-stimulatory 4-1BB ligand. The memory-like state was by stimulating either PBNK sample group with IL-12, IL-15, and IL-18 for 16 hours and compared with non-preactivated magnetically isolated or mbIL-21/4-1BB K562 co-cultured and expanded NK cells. We observed that Magnetic bead-isolated NK cells clearly separated into preactivated and non-preactivated clusters in contrast to IL21/4-1BB K562 expanded NK cells which exhibited methylation patterns mailnly mimicking epigenetic features of preactivated magnetic bead-isolated PBNK cells. Thus, The pre-activation along with IL21/4-1BB K562 co-culture led to the hypomethylation of CpG regions across various gene loci, suggesting a strong and extensive epigenetic reaction that promotes a transcriptionally permissive chromatin state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268065 | GEO | 2025/03/14

REPOSITORIES: GEO

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Memory-like natural killer cell and CD19-antibody based immunotherapy in combination with tyrosine-kinase inhibition of Ph(-like) acute lymphoblastic leukemia (RNA-Seq)

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