Abstract
Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
Highlights
Immune cells constantly monitor the body to eliminate nascent transformed cells, a process known as immunosurveillance [1, 2]
We report that Mo-Myeloid-derived suppressor cells (MDSCs) significantly increase in the peripheral blood of breast cancer patients with locoregional recurrence or metastatic breast cancer (LRR/MBC) and correlate with increased metastasis to lymph nodes and visceral organs, suggesting that circulating Mo-MDSCs are a potential biomarker for disease progression
The Mo-MDSC surface phenotype was increasingly pronounced with disseminated disease, the monocytes from patients with early, primary, breast cancer were affected functionally
Summary
Immune cells constantly monitor the body to eliminate nascent transformed cells, a process known as immunosurveillance [1, 2]. As a tumor progresses the immune response is modulated by the tumor, resulting in non-responsiveness towards the tumor cells. The presence of local immunosuppressive cells correlate with poor prognosis in various forms of malignancies [3,4,5,6,7,8,9]. These populations contribute to a local immunosuppression at the site of the PLOS ONE | DOI:10.1371/journal.pone.0127028. These populations contribute to a local immunosuppression at the site of the PLOS ONE | DOI:10.1371/journal.pone.0127028 May 20, 2015
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