Abstract
OBJECTIVE: To investigate the impact of neoadjuvant hormonal therapy (NHT) on interleukin‑17 A (IL‑17 A) signaling and inflammation in prostate cancer (PCa), and to explore the role of the IL‑17 A/signal transducer and activator of transcription 3 (STAT3) axis in tumor progression after androgen deprivation. METHODS: Paired prostate tissue samples from 27 patients receiving ≥ 3 months of NHT were analyzed. Histological inflammation was assessed by hematoxylin-eosin staining. Immunohistochemistry was used to evaluate IL-17 A, interleukin‑17 receptor A (IL‑17RA), interleukin‑17 receptor C (IL‑17RC), STAT3, and androgen receptor (AR). Statistical analyses were performed to examine differences in expression and correlations between markers. RESULTS: Chronic inflammation significantly increased in tumor tissues after NHT (P < 0.05). IL-17 A and IL-17RC expression were higher in tumor tissues than adjacent benign tissues (P < 0.001), with further upregulation after NHT (P < 0.05). Longer NHT duration (≥ 6 months) was associated with elevated IL-17 A and IL-17RC levels. IL-17 A expression positively correlated with STAT3 (r = 0.388, P = 0.045), but not with androgen receptor (AR). CONCLUSIONS: Prolonged NHT enhances IL-17 A/IL-17RC-mediated inflammation in prostate cancer, potentially promoting tumor progression through STAT3 activation. Targeting the IL-17 A/STAT3 axis may offer therapeutic potential for advanced prostate cancer, although further validation is required before NHT can be incorporated into clinical guidelines.