Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide

Purpose: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer (PCa), with poor immunogenicity and subsequent low PD-L1 expression in PCa being proposed as an explanation. However, recent studies indicate that a subset of PCa may express significant levels of PD-L1. Further, the androgen antagonist enzalutamide has been shown to up-regulate PD-L1 expression in PCa preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in PCa. Experimental Design: Radical prostatectomy (RP) tissues were collected from 44 patients with intermediate-to-high risk PCa who underwent RP after Neo-AAPL treatment. Untreated PCa tissues were collected from 130 patients, including 44 matched controls for the Neo-AAPL cases. Tumor PD-L1 expression was detected by immunohistochemistry using validated anti-PD-L1 antibodies. Tumor-infiltrating CD8+ cells were analyzed in trial cases and matched controls. Expression of DNA mismatch repair genes was examined in PD-L1-positive tumors. Results: Neo-AAPL-treated tumors showed a trend toward decreased PD-L1 positivity compared to matched controls (7% vs 21% having ≥1% positive tumor cells; p = 0.062). Treated tumors also harbored significantly less tumor-infiltrating CD8+ cells (p = 0.029). In 130 untreated PCas, African American, elevated serum PSA, and small prostate independently predicted tumor PD-L1 positivity. Loss of MSH2 expression was observed in one of twenty-one PD-L1-positive tumors. Conclusions: A subset of PCa expresses PD-L1, which is not increased by Neo-AAPL treatment, indicating that combining Neo-AAPL treatment with PD-L1/PD-1 blockade may not be synergistic.

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