Immune-metabolic plasticity in AML: Prognostic roles of aCTLs (activated Cytotoxic T Cells) and Kynurenine.

Acute myeloid leukemia (AML), traditionally risk-stratified by genetic abnormalities, is an aggressive malignancy with high relapse and modest survival. Immune dysregulation is an emerging pathogenic mechanism. We investigated cellular immune subsets and metabolic mediators of the PD-L1/PD-1 and IDO1-kynurenine-AhR pathways, including vitamin D as an immunomodulatory component in 78 newly diagnosed adult AML uniformly treated with intensive therapy. Lower TLC (<30 × 109/L) and blast percentage (<67%) were associated with higher CR rates (OR=3.9, p = 0.006; OR=2.9, p = 0.025). Higher baseline activated cytotoxic-T-cells (aCTLs; CD8+ PLCγ1+) predicted better OS (18-month OS 60.9% vs. 32.2%; p = 0.023). Other baseline clinical, vitamin D, and immune parameters were not associated with OS or LFS. Post-induction, kynurenine and Treg/CTL ratio increased, while tryptophan, aCTLs, and aTreg/aCTL ratio decreased. Higher post-treatment kynurenine was associated with better OS (30% vs. 64%; p = 0.017) and LFS (44% vs. 71%; p = 0.09). These findings highlight complex, plastic immune interactions in AML with potential prognostic and therapeutic implications. Micro-abstract: This study in de novo acute myeloid leukemia (AML) demonstrates that higher baseline activated cytotoxic T cells (CD8+PLCγ1+) and increased post-induction kynurenine are novel prognostic markers associated with improved survival after intensive chemotherapy. Chemotherapeutic treatment induces dynamic immune-metabolic changes, underscoring the importance of integrating immune profiling into clinical AML management.