The Interplay of PD-L1, Kynurenine Pathway, and Vitamin D Shapes an Immunosuppressive Microenvironment in Acute Myeloid Leukemia

BACKGROUND: Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy. However, the immune microenvironment-including immune checkpoint pathways and metabolic regulators also plays a pivotal role in disease progression. AIMS: To investigate the immune-metabolic landscape of newly diagnosed AML patients, focusing on the PDL1-PD1 and IDO-Kynurenine-AhR pathways, and their association with vitamin D levels. SETTING: A prospective, observational study conducted at a tertiary care academic hospital. MATERIALS: A total of 127 newly diagnosed AML patients were enrolled. Flow cytometry was used to assess PD-L1 expression on blasts and immune T cell subsets. Serum levels of tryptophan, kynurenine, and vitamin D were measured using enzyme-linked Immunosorbent Assay (ELISA) and Chemiluminescent Immunoassay (CLIA). STATISTICS: Correlation analysis and chi-square test/Mann-Whitney U test were applied. A p-value <0.05 was considered significant. RESULTS: PDL1 expression on blasts inversely correlated with CD8+ T cells (p=0.044), indicating immune evasion. CD3+ positively correlated with CD8+ T cells (p=0.007), while CD4+ negatively correlated with CD8+ T cells (p<0.001), suggesting divergent immune roles. Elevated tryptophan/kynurenine correlated with increased PD1+CD4+ T cells (p=0.039), which in turn were associated with higher Treg frequencies (p=0.001). Low vitamin D levels were associated with higher odds of aTregs (OR 2.7; 95% CI 1-7). CONCLUSIONS: An immunosuppressive microenvironment in AML is driven by PD-L1 expression, kynurenine pathway activation, and low vitamin D levels. These findings suggest potential immunotherapeutic targets and highlight vitamin D's immunomodulatory role.