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

• Published in: Clinical cancer research Vol. 23; no. 22; pp. 6812 - 6822
• Main Authors: Calagua, Carla, Russo, Joshua, Sun, Yue, Schaefer, Rachel, Lis, Rosina, Zhang, Zhenwei, Mahoney, Kathleen, Bubley, Glenn J., Loda, Massimo, Taplin, Mary-Ellen, Balk, Steven P., Ye, Huihui
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.11.2017
• Subjects: Abiraterone Acetate - administration & dosage; Acetic acid; Androgens; Antibodies; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cancer; Cancer surgery; CD8 antigen; Cell death; Deoxyribonucleic acid; Deprivation; DNA; DNA Mismatch Repair; DNA repair; Experimental design; Gene Expression; Health risks; Humans; Immunogenicity; Immunohistochemistry; Leuprolide - administration & dosage; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Minority & ethnic groups; Mismatch repair; MSH2 protein; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Patients; PD-1 protein; PD-L1 protein; Prednisone; Prednisone - administration & dosage; Prostate cancer; Prostatectomy; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Tissues; Tumor cells; Tumors
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-0807

Purpose: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer, with poor immunogenicity and subsequent low PD-L1 expression in prostate cancer being proposed as an explanation. However, recent studies indicate that a subset of prostate cancer may express significant levels of PD-L1. Furthermore, the androgen antagonist enzalutamide has been shown to upregulate PD-L1 expression in prostate cancer 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 prostate cancer. Experimental Design: Radical prostatectomy (RP) tissues were collected from 44 patients with intermediate- to high-risk prostate cancer who underwent RP after Neo-AAPL treatment. Untreated prostate cancer tissues were collected from 130 patients, including 44 matched controls for the Neo-AAPL cases. Tumor PD-L1 expression was detected by IHC 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 with matched controls (7% vs. 21% having ≥1% positive tumor cells; P = 0.062). Treated tumors also harbored significantly fewer tumor-infiltrating CD8+ cells (P = 0.029). In 130 untreated prostate cancers, African American ethnicity, elevated serum PSA, and small prostate independently predicted tumor PD-L1 positivity. Loss of MSH2 expression was observed in 1 of 21 PD-L1–positive tumors. Conclusions: A subset of prostate cancer 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. Clin Cancer Res; 23(22); 6812–22. ©2017 AACR.