Divergent roles of PKM2 in regulating PD-L1 and PD-L2 expression and their implications in human and mouse cancer models

• PKM2 exerts divergent regulation on immune checkpoints: it enhances PD-L1 expression while inhibiting PD-L2, promoting immune evasion. • GATA3 is identified as a key transcription factor mediating PKM2's effects, directly binding to PD-L1 and PD-L2 promoters. • In ESCC, PKM2 mRNA negatively correlates with CD8+ T-cell infiltration, suggesting a role in modulating the tumor immune microenvironment. • Targeting the PKM2-GATA3 axis may provide a novel strategy to fine-tune PD-L1 and PD-L2 levels and enhance cancer immunotherapy.