MODULATION OF PD-L1 EXPRESSION IN PROSTATE CANCER CELLS THROUGH ANDROGEN RECEPTOR INHIBITION DIFFERS DEPENDING ON RECEPTOR STATUS
DOI:
https://doi.org/10.15407/exp-oncology.2025.01.060Keywords:
prostate cancer, PD-L1, androgen, androgen receptor, enzalutamideAbstract
Background. Immune checkpoint blockade (ICB) therapy targeting the PD-1/PD-L1 axis results in poor outcomes in prostate cancer (PCa). PD-L1, the most commonly used predictive marker for the efficacy of PD-1/PD-L1-targeted immunotherapy, appears to be rarely or at low levels expressed in primary androgen-responsive PCa tumors, with higher levels in advanced PCa. PD-L1 expression has not yet been studied regarding the androgen receptor (AR) status. Materials and Methods. We investigated the effect of hormone stimulation by dihydrotestosterone (DHT) and AR inhibition by enzalutamide on PD-L1 expression in LNCaP and LNCaP-AR+ cells, the latter overexpressing AR. Cells were grown for 24 h under hormone-free conditions and then for 24 h in the presence of DHT (10 nM) and/or enzalutamide (10 μM). Cell viability was assessed by Annexin V and propidium iodi de staining. PD-L1 expression was determined semiquantitatively at the mRNA level. ANOVA and independent t-tests were used to compare experimental results between different treatment modalities. Results. DHT treatment induced some degree of apoptosis in AR-overexpressing LNCaP-AR + cells, but not in parental LNCaP cells. We found low basal expression of PD-L1 in both cell lines, with 2.7-fold higher levels in LNCaP-AR+ cells. DHT treatment increased PD-L1 expression by approximately three-fold in LNCaP cells, while in enzalutamide-treated cells, the expression was lower than the basal level. In LNCaP cells treated concomitantly with DHT and enzalutamide, AR inhibition reduced DHT-induced PD-L1, suggesting an androgen-dependent expression of PD-L1. Unlike in LNCaP cells, androgen stimulation did not increase PD-L1 expression in LNCaP-AR+ cells, and enzalutamide did not affect PD-L1 expression either. Conclusion. Our data reveal that PD-L1 is expressed in an AR-dependent manner in PCa cells, and its expression in AR-overexpressing cells is not modulated by receptor inhibition.
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