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Breast Cancer Research and Treatment

, Volume 140, Issue 1, pp 13–21 | Cite as

Myeloid-derived suppressor cells in breast cancer

  • Joseph Markowitz
  • Robert Wesolowski
  • Tracey Papenfuss
  • Taylor R. Brooks
  • William E. CarsonIII
Review

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.

Keywords

Breast cancer Myeloid-derived suppressor cells Therapy Murine models 

Notes

Acknowledgments

We would like to acknowledge T32CA090223 (to J. Markowitz). Taylor Brooks was supported by the Pelotonia undergraduate fellowship Program. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the Pelotonia Fellowship Program. We would also like to acknowledge P01CA095426.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Joseph Markowitz
    • 1
  • Robert Wesolowski
    • 2
  • Tracey Papenfuss
    • 3
  • Taylor R. Brooks
    • 4
  • William E. CarsonIII
    • 5
  1. 1.Division of Medical OncologyThe Ohio State UniversityColumbusUSA
  2. 2.Division of Medical OncologyThe Ohio State UniversityColumbusUSA
  3. 3.Department of Veterinary BiosciencesThe Ohio State UniversityColumbusUSA
  4. 4.Laboratory of Dr. William CarsonThe Ohio State UniversityColumbusUSA
  5. 5.OSU Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA

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