Glucocorticoids Downregulate PD-L1 Expression in Glioblastoma Cells via GILZ-Dependent Inhibition of the ERK Pathway

Glucocorticoids (GCs), such as dexamethasone (DEX), are commonly administered to glioblastoma (GBM) patients to control cerebral edema; however, their effects on immune checkpoint regulation in tumor cells remain insufficiently characterized. This study ex-amined the impact of DEX on the expression of programmed death-ligand 1 (PD-L1) and glucocorticoid-induced leucine zipper (GILZ), a downstream effector of glucocorticoid re-ceptor (GR) signaling, in the U87 and U251 glioblastoma cell lines. DEX consistently in-duced GILZ expression in both models yet elicited divergent effects on PD-L1: suppression in U87 cells and upregulation in U251 cells. In U87 cells, DEX-induced PD-L1 downregu-lation was accompanied with accelerated cell cycle progression, suggesting a dual impact on tumor immune evasion and proliferation. Mechanistically, GILZ silencing restored ERK phosphorylation and reversed PD-L1 suppression, whereas GILZ overexpression further decreased PD-L1 levels, implicating a GILZ–ERK pathway in the control of PD-L1. These findings uncover a previously unrecognized GR–GILZ–PD-L1 regulatory axis in glioblastoma cells. While these results are based on in vitro models, they provide a ra-tionale for future vivo studies to determine whether modulation of GILZ may influence immune checkpoint dynamics and therapeutic responsiveness in glioblastoma.