Elevated Circulating Myeloid Derived Suppressor Cells (MDSC) Are Associated with Inferior Overall Survival (OS) and Correlate with Circulating Tumor Cells (CTC) in Patients with Metastatic Breast Cancer.

Abstract

Abstract Background: MDSC acumulation is an important mechanism of tumor escape from immune surveillance and cancer progression. Pre-clinical studies have shown a correlation between tumor progression and MDSC. While we and others have shown that circulating MDSC correlate with clinical stage, to date there are few clinical studies that have explored the correlation of MDSC with metastatic tumor burden or as an adverse prognostic factor. Consequently, the goal of this study was to determine whether levels of MDSC in patients with stage IV breast cancer correlate with tumor burden using CTC and Swenerton Scores (SS) as surrogates for metastatic disease burden, and if circulating MDSC levels were predictive of overall survival.Methods: Flow cytometric analysis was performed on peripheral whole blood from 25 patients with stage IV breast cancer prior to initiation of therapy and at defined intervals during therapy. The MDSC population was defined as lineage-, CD33+, HLA-DR-, CD11b+. CTC (CellSearch®) and MDSC were drawn simultaneously and SS were calculated using a standardized scoring system previously defined and published in the literature. A generalized estimating equation regression model was created and fitted individually for each predictor. OS was defined as time of study enrollment to date of death.Results: Using a generalized estimating equation regression model the percentage of MDSC in peripheral blood was found to have a close correlation with CTC (Pearson correlation 0.62, p=0.0001) and a coefficient of 0.29 (0.14, 0.43 95%CI). The correlation between percent MDSC and SS was not significant (Pearson 0.31, p=0.12). Interestingly, no significant correlation between CTC and SS was noted either. MDSC levels were also found to predict OS in patients with the highest percentages at the first visit having significantly decreased median overall survival [6.8 vs. 19.6 months; p=0.05]Similarly, high MDSC levels at the final blood draw was also found to correlate with significantly shorter median OS [p=0.023].Conclusions. MDSC correlated well with CTC but not SS. High circulating MDSC levels were associated with significantly decreased overall survival in patients with metastatic breast cancer. MDSC appear to be a promising prognostic immunologic biomarker in metastatic breast cancer. Further studies are needed to better define the role of MDSCs in breast cancer progression and may be a useful therapeutic target to enhance the effectiveness of immune based therapies in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4135.