Brief Communication: LSD1 Inhibition Enhances Susceptibility of Primary AML Cells for NK Cell-Mediated Killing

Acute myeloid leukemia (AML) is a hematological malignancy associated with poor prognosis. Recent developments in natural killer (NK) cell-based immunotherapies have resulted in the robust expansion of NK cells with enhanced cytotoxicity against hematological malignancies. However, disease relapse remains a challenge. Another therapeutic intervention that has garnered high interest is the use of lysine-specific demethylase 1 (LSD1) inhibitors for AML treatment. Here, we investigated whether LSD1 inhibition could synergize with ex vivo expanded NK (exNK) cells in a primary AML sample. Interestingly, we observed that treatment with the LSD1 inhibitors, bomedemstat and GSK-LSD1, led to the upregulation of multiple stress ligands known to activate NK cells. Importantly, this increased stress ligand expression was associated with enhanced NK cell-mediated cytotoxicity, suggesting the potential for both therapies to be used synergistically. To our knowledge, this is the first study to assess the combination of LSD1 inhibition and exNK cells in AML.