Boosting antileukemia cytotoxicity of CD4 and CD8 T cells through combined inhibition of MEK and HDAC.

Combined trametinib and quisinostat (TQ) potently suppresses growth of NRAS/ASXL1-driven, MLL-rearranged, and NPM1-mutated AML cells and improves survival in NA-AML mice.

• Why it matters: AML has limited response to T-cell–engaging immunotherapies, so strategies that restore effective T-cell recognition and killing are urgently needed.
• What they did: A drug repurposing screen identified TQ, and in NA-AML mice the study assessed tumor progression, survival, T-cell dependence, checkpoint ligand changes, MHC-I/II regulation, and T-cell transcriptome/epigenetic reprogramming.
• The result: TQ slowed AML progression and prolonged survival in NA-AML mice, with benefits largely relying on T-cell functions, expanding cytotoxic CD4/CD8 memory subsets and enhancing MHC-dependent leukemia killing in cocultures.

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