PD-L1 Expression in Acute Myeloid Leukemia Cells: Associations With Cell Metabolism

The programmed death ligand 1 (PD-L1) is a prominent mediator of immune system inhibition in various cancer types. In acute myeloid leukemia (AML), the prognostic meaning of PD-L1 expression is still unclear and likely depends on the mechanism of its induction. We analyzed PD-L1 expression (transcript and protein) in primary cells of patients with AML at diagnosis as a function of cell metabolic phenotype. The percentage of PD-L1-positive cells was typically low shortly after cell isolation but increased after overnight rest, in correlation with the cell glycolysis rate. The increase in PD-L1 was prevented by pharmacological inhibition of the transcription factor STAT3 or pyruvate kinase M2 (PKM2) while JAK1/2 inhibition by ruxolitinib was less efficient. PD-L1 positivity in freshly isolated cells was associated with increased levels of plasma IL-6 and IL-18. Furthermore, glycolytic primary cells induced PD-L1 on cocultured AML cell lines. Although PD-L1 was present at variable levels in exosomes released from primary cells, no correlation between the exosomal PD-L1 and PD-L1 on cocultured cells was observed. Our results suggest that PD-L1 expression in leukemia cells is highly dynamic and regulated by PKM2/STAT3. Bulk AML cells can induce PD-L1 on more primitive leukemia cells and support their immune evasion.