Myeloid-derived suppressor cells in breast cancer

• Published in: Breast cancer research and treatment 2013-07, Vol.140 (1), p.13-21
• Main Authors: Markowitz, Joseph, Wesolowski, Robert, Papenfuss, Tracey, Brooks, Taylor R., Carson, William E.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - psychology; Cancer research; Cancer therapies; Cytokines; Cytokines - metabolism; Disease Models, Animal; Female; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Humans; Immunotherapy; Immunotherapy - methods; Intercellular Signaling Peptides and Proteins - metabolism; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Transgenic; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Myeloid Cells - drug effects; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - pathology; Oncology; Oncolytic Virotherapy - methods; Predictive Value of Tests; Reactive Oxygen Species - metabolism; Review; Stress, Psychological; T cell receptors; T cells; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-013-2618-7

Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells defined by their suppressive actions on immune cells such as T cells, dendritic cells, and natural killer cells. MDSCs typically are positive for the markers CD33 and CD11b but express low levels of HLADR in humans. In mice, MDSCs are typically positive for both CD11b and Gr1. These cells exert their suppressive activity on the immune system via the production of reactive oxygen species, arginase, and cytokines. These factors subsequently inhibit the activity of multiple protein targets such as the T cell receptor, STAT1, and indoleamine-pyrrole 2,3-dioxygenase. The numbers of MDSCs tend to increase with cancer burden while inhibiting MDSCs improves disease outcome in murine models. MDSCs also inhibit immune cancer therapeutics. In light of the poor prognosis of metastatic breast cancer in women and the correlation of increasing levels of MDSCs with increasing disease burden, the purposes of this review are to (1) discuss why MDSCs may be important in breast cancer, (2) describe model systems used to study MDSCs in vitro and in vivo, (3) discuss mechanisms involved in MDSC induction/function in breast cancer, and (4) present pre-clinical and clinical studies that explore modulation of the MDSC–immune system interaction in breast cancer. MDSCs inhibit the host immune response in breast cancer patients and diminishing MDSC actions may improve therapeutic outcomes.