ALDH1 inhibition by DIMATE maintains immune responses and promotes immunogenic remodeling in AML.

Acute myeloid leukemia (AML) treatments often cause profound immunosuppression, limiting immune-mediated control of residual disease. DIMATE, an ALDH1 inhibitor under clinical evaluation, induces aldehyde and redox stress in leukemic cells, but its impact on immune effector functions and tumor immunogenicity remains insufficiently defined. Here, we assessed the effects of DIMATE on human immune cells and AML models, including peripheral blood mononuclear cells, AML cell lines, and primary AML samples. DIMATE largely preserved selected immune effector functions at pharmacologically relevant concentrations, including T-cell activation, natural killer cell cytotoxicity, and phagocyte oxidative burst. In parallel, DIMATE induced pro-inflammatory and endoplasmic reticulum stress pathways in AML cells, upregulated co-stimulatory molecules, and promoted ICD-compatible features, including ecto-calreticulin exposure. These findings suggest that DIMATE may couple immune preservation with enhanced leukemic immunogenicity, supporting its potential for combination with immune-engaging therapies and strategies targeting measurable residual disease in AML, but also as a single agent capable of fostering a more immunostimulatory anti-leukemic context.