Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy
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Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I–IV). Percentages of circulating MDSC (Lin−/Lo, HLA DR−, CD33+CD11b+) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.
KeywordsImmature myeloid cells Myeloid-derived suppressor cells Breast cancer Cancer Cyclophosphamide Tumor burden Cytokines PBMC T cells
The authors would like to thank Amir Al Khami, Tracy Vandenberg, and Steven Hutchens for technical support, and Kristi Vissage for data analysis. Special thanks to Paolo Serafini for critical review of the manuscript. This work was supported in part by a Chain Reaction for the Cure Grant http://www.chainreactionforacure.org/, a seed grant from Hollings Cancer Center and R01CA83672. Funding sources has no involvement in any aspect of conducting this research, data analysis, or manuscript preparation for publication.
Conflict of interest statement
Authors declare no conflicts of interest.
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