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Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250
Many cancer immunotherapies developed in experimental animals have been tested in clinical trials. Although some have shown modest clinical effects, most have not been effective. Recent studies have identified myeloid-origin cells that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. "Myeloid-derived suppressor cells" (MDSC) accumulate in the blood, lymph nodes, and bone marrow and at tumor sites in most patients and experimental animals with cancer and inhibit both adaptive and innate immunity. MDSC are induced by tumor-secreted and host-secreted factors, many of which are proinflammatory molecules. The induction of MDSC by proinflammatory mediators led to the hypothesis that inflammation promotes the accumulation of MDSC that down-regulate immune surveillance and antitumor immunity, thereby facilitating tumor growth. This article reviews the characterization and suppressive mechanisms used by MDSC to block tumor immunity and describes the mechanisms by which inflammation promotes tumor progression through the induction of MDSC.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01CA115880 and R01CA84232 and by the Susan G. Komen for the Cure Foundation.
2 Address correspondence and reprint requests to Dr. Suzanne Ostrand-Rosenberg, Department Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250. E-mail address: srosenbe{at}umbc.edu
3 Abbreviations used in this paper: ROS, reactive oxygen species; COX, cyclooxygenase; DC, dendritic cell; iNKT, invariant NKT; MDSC, myeloid-derived suppressor cell; Treg, regulatory T cell; VEGF, vascular endothelial growth factor.
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