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

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Programmed death ligand 1 (PD-L1) is crucial for immune suppression in cancers.
• The role and regulation of PD-L1 in acute myeloid leukemia (AML) remain incompletely understood.
• PD-L1 induction mechanisms may vary, impacting its prognostic significance in AML.

Purpose of the Study:

• To investigate the regulation of PD-L1 expression in primary AML cells.
• To correlate PD-L1 levels with cellular metabolic phenotypes.
• To identify key molecular regulators of PD-L1 expression in AML.

Main Methods:

• Analysis of PD-L1 transcript and protein in diagnostic AML samples.
• Assessment of PD-L1 expression in relation to cellular glycolysis.
• Pharmacological inhibition of STAT3, PKM2, and JAK1/2 pathways.
• Co-culture experiments with primary AML cells and AML cell lines.
• Measurement of plasma IL-6 and IL-18 levels.
• Exosome isolation and analysis.

Main Results:

• PD-L1 expression increased after overnight culture, correlating with glycolysis.
• Inhibition of PKM2 and STAT3 prevented PD-L1 upregulation; ruxolitinib was less effective.
• Freshly isolated AML cells with PD-L1 positivity showed higher IL-6 and IL-18 levels.
• Glycolytic AML cells induced PD-L1 expression in co-cultured AML cell lines.
• Exosomal PD-L1 did not correlate with PD-L1 on co-cultured cells.

Conclusions:

• PD-L1 expression in AML is dynamic and metabolically regulated.
• The PKM2/STAT3 pathway is a key regulator of PD-L1 induction in AML.
• Bulk AML cells can promote immune evasion in more primitive leukemia cells via PD-L1 induction.