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Review
. 2015:2015:159269.
doi: 10.1155/2015/159269. Epub 2015 May 19.

Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

Hiroshi Katoh  1 , Masahiko Watanabe  1
Affiliations
Review

Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

Hiroshi Katoh et al. Mediators Inflamm. 2015.

Abstract

Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

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Figures

Figure 1
Figure 1
Surface markers and suppressive mechanisms of MDSCs. In murine cancer models, G-MDSCs (CD11b+Ly6GhiLy6Clo) and M-MDSCs (CD11b+Ly6ChiLy6G−) can be discriminated by the cell surface markers. However, identifying human MDSCs is still challenging because of their phenotypic heterogeneity and the absence of cognate surface markers in mice. Generally, human MDSCs can be defined as CD11b+CD33+Lin−/loHLA-DR−/lo and further divided to CD15+ or CD66b+ G-MDSCs and CD14+ M-MDSCs. A substantial population shows both CD15 (or CD66b) and CD14 negative, suggesting that G-MDSCs and M-MDSCs are not completely distinct population. M-MDSCs can differentiate mature dendritic cells and macrophages or putatively G-MDSCs.
Figure 2
Figure 2
Schema of MDSC expansion and recruitment machinery. Tumor-derived factors (e.g., GM-CSF, IL-6, S100A8/A9, and PGE2) promote proliferation, expansion, and mobilization of MDSCs from bone marrow hematopoietic progenitor cells, and tumor-derived chemokines (e.g., CXCL1/2 and CXCL12) recruit MDSCs to primary tumor and metastatic niche according to their chemokine gradients. Bone marrow-derived MDSC precursors are also arrested at marginal zone of spleen and migrate to the red pulp and proliferate. Recruited MDSCs support tumor progression by the immunosuppressive activities against cytotoxic CD8+ T cells and NK cells. M-MDSCs can differentiate to mature nonsuppressive dendritic cells or type 1 macrophages. MDSCs also facilitate tumor-associated angiogenesis and epithelial-mesenchymal transition of cancer cells, which results in invasion and extravasation. On the other hand, MDSCs can contribute to mesenchymal-epithelial transition at the metastatic niche.
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References

    1. Coussens L. M., Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–867. doi: 10.1038/nature01322. - DOI - PMC - PubMed
    1. Orimo A., Gupta P. B., Sgroi D. C., et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 2005;121(3):335–348. doi: 10.1016/j.cell.2005.02.034. - DOI - PubMed
    1. Katoh H., Hosono K., Ito Y., et al. COX-2 and prostaglandin EP3/EP4 signaling regulate the tumor stromal proangiogenic microenvironment via CXCL12-CXCR4 chemokine systems. The American Journal of Pathology. 2010;176(3):1469–1483. doi: 10.2353/ajpath.2010.090607. - DOI - PMC - PubMed
    1. Gabrilovich D. I., Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology. 2009;9(3):162–174. doi: 10.1038/nri2506. - DOI - PMC - PubMed
    1. Ostrand-Rosenberg S., Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. The Journal of Immunology. 2009;182(8):4499–4506. doi: 10.4049/jimmunol.0802740. - DOI - PMC - PubMed

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