Immune characterization of the programmed death receptor pathway in high-risk prostate cancer.

Abstract

40 Background: Programmed Death 1 (PD-1) is a T cell inhibitory receptor critical to a major immunomodulation pathway which has been implicated in tumor evasion of immune response. PD-1 and its ligand PD-L1 have been found to be expressed in many tumor types, and this expression has led to the development of drugs targeting the PD-1 pathway. The goal of this study was to understand the expression of PD-1, and PD-L1 in high grade prostate cancer tissue, and correlate the expression with disease and patients characteristics. Methods: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed on prostatectomy/biopsy tissue samples taken from 25 men with high grade (Gleason 8-10) prostate cancer using anti-PD-L1 clone 22C3 (Merck) and anti-PD-1 clone NAT105 (Cell Marque) . CD3 was used as a specific marker for T cell infiltration. Charts were then retrospectively reviewed for patient and disease characteristics including age at diagnosis, race, Gleason score, prostatic specific antigen (PSA) level at diagnosis, number of positive cores at biopsy, volume of tissue on biopsy and/or prostatectomy involved by cancer, clinical TNM stage, pathologic TNM stage, biochemical recurrence, or metastasis. Statistical analyses were done to correlate these patient and disease characteristics with PD-1, PD-L1, and CD3 expression. Results: A score of 3-5 on the semi-quantitative 0-5 score was deemed “high” expression whereas a score of 0-2 was deemed “low” expression. Of the 25 samples, 2 (8%) scored high for PD-1 expression, 2 (8%) scored high for PD-L1 expression, and 18 (72%) scored high for CD3 expression. With independent t-tests there was found to be no statistically significant correlation between any of the variables we collected and expression of PD-1, PD-L1, or CD3. Conclusions: We found an overall low expression of PD-1 and PD-L1, and a concurrent high expression of CD3+ T cells in high risk prostate cancer tissue. No significant correlations were made between expression of PD-1, PD-L1, or CD3 and patient and disease characteristics. The elevated T cell content in high risk prostate cancer is particularly interesting with the continued emergence of new drugs focused on enhancing efficacy of the immune response in cancer.