Hypoxia and Serum Factor Modulate B7-H3 Expression in Prostate Cancer Cells

Background: Data on the expression and regulation of immune checkpoint inhibitors in prostate tissue and cells remain limited. This study aims to characterize the expression and regulatory mechanisms of B7-H3 (CD276) in prostate tissues and cell models. Methods: In silico analyses were performed to evaluate the expression of B7-H3 and other checkpoint inhibitors in prostate tissues and cell lines. In vitro experiments assessed the impact of tumor microenvironmental factors on B7-H3 expression. Results: B7-H3 was identified as the most abundant checkpoint inhibitor in prostate tissues and cell lines. Its expression was highest in androgen-responsive LNCaP cells compared to other commonly used prostate cancer models. Hypoxic conditions and charcoal dextran-treated serum (CDS) significantly reduced B7-H3 mRNA and protein levels in LNCaP cells but not in androgen-independent DU145 or PC3 cells. Conversely, dihydrotestosterone (DHT) did not influence B7-H3 expression. Conclusion: B7-H3, rather than other checkpoint inhibitors, may play a critical role in prostate cancer tumorigenesis. Hypoxia, rather than androgen signaling, appears to regulate B7-H3 expression, and this regulatory response may be lost in more aggressive androgen-independent prostate cancer cells.