title: Myeloid-derived suppressor cells in breast cancer.
abstract: 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.
authors.affiliation: Division of Medical Oncology, The Ohio State University, 320 W. 10th Ave., Columbus, OH 43210, USA. joseph.markowitz@osumc.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Markowitz
authors.forename: Robert
authors.initials: R
authors.lastname: Wesolowski
authors.forename: Tracey
authors.initials: T
authors.lastname: Papenfuss
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Brooks
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000523:psychology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D050130:Oncolytic Virotherapy / Q000379:methods; D011237:Predictive Value of Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D013315:Stress, Psychological; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species