Presence of myeloid-derived suppressor cells (MDSC) in patients with metastatic castration-sensitive and castration-resistant prostate cancer.

Abstract

222 Background: MDSC contribute to an immune suppressive environment and have been implicated in cancer progression. Measurement (identification and enumeration) is challenged by the lack of analytically valid assays limiting data interpretation between groups. This impacts our understanding of rationale immune targets and design of clinical trials. We employed a novel biomarker based assay in whole blood to enumerate MDSC from patients with metastatic castration sensitive (CSPC) and castration resistant prostate cancer (CRPC). Methods: Whole blood was collected in Cyto-Chex (Streck) tubes. A published computational algorithm-based approach (developed by Memorial Sloan Kettering Cancer Center and commercialized by Serametrix) was employed to determine the %MDSC-monocytic and coefficient of variance (CV=ratio of SD and geometric mean fluorescence intensity) to assess HLA-DR spread on CD14+CD11b cells. Samples were performed in duplicate. Clinical variables including clinical state, past and current treatment, metastatic sites, PSA, and standard prognostic markers were collected. Results: 36 pts with metastatic prostate cancer (29 CRPC; 7 CSPC) were included. Median (SD) %MDSC in 29 CRPC pts was 21.15 (5.33) and median (SD) CV was1.29 (0.25); 7 CSPC demonstrated a median (SD) %MDSC 19.15 (4.86) and median (SD) CV 1.22 (0.25). MDSC did not differ between chemotherapy exposed (n=13) and chemotherapy naive (n=16) CRPC (23.3 vs 19.5, p=ns). MDSC were not significantly higher in those with visceral mets, though a trend existed (20.3 vs 24.0, p=0.076). PSA did not appear to correlate with MDSC or CV. Conclusions: Understanding the distribution and characterization of MDSC in various clinical states in prostate cancer is relevant to the development of immune targets in this disease. MDSC were quantifiable in both CSPC and CRPC. There was a trend for higher MDSC values in patients with visceral metastases, which historically are associated with worse prognoses. Presence of MDSC in metastatic CSPC and CRPC has important therapeutic and trial implications. Further discovery in larger cohorts and earlier disease states is underway.