The success of cellular therapies in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) indicates leukemic cells are immune-sensitive when targeted appropriately. In a phase Ib clinical trial (NCT03066648), we profiled longitudinal bone marrow and peripheral blood samples from AML/MDS patients treated with the anti-TIM3 antibody sabatolimab in combination with the hypomethylating agent decitabine,employing single cell RNA+TCRαβ sequencing and flow cytometry alongside functional co-culture assays.Unlike CTLA4 and PD1, which are primarily restricted to T cells, TIM3 was broadly expressed across NK, myeloid and T cell populations. Therapy induced expansion of cytotoxic CD56dim and adaptive NK cell subsets, accompanied by robust type I interferon signaling, which was associated with reduced risk of relapse. Notably, phenotypically exhausted CD8+ T cells constituted a minor fraction (2 years) harbored CD4+ T cell large granular lymphocyte leukemia (T-LGLL) cells bearing TCRs targeting autologous AML blasts demonstrated by functional co-culture assays.