Myeloid-Derived Suppressor Cells Regulate Growth of Multiple Myeloma by Inhibiting T Cells in Bone Marrow.

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612.
The Journal of Immunology (Impact Factor: 5.36). 03/2013; 190(7). DOI: 10.4049/jimmunol.1203373
Source: PubMed

ABSTRACT Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the immune response in cancer. However, their role in bone marrow (BM), the site of primary localization of multiple myeloma (MM), is poorly understood. In this study, we found a significant accumulation of CD11b+CD14-CD33+ immunosuppressive MDSC in BM of patients with newly diagnosed MM. To assess the possible role of MDSC in MM, we used immunocompetent mouse models. Immunosuppressive MDSC accumulated in BM of mice as early as 1 wk after tumor inoculation. S100A9 knockout (KO) mice, which are deficient in their ability to accumulate MDSC in tumor-bearing hosts, demonstrated reduced MDSC accumulation in BM after injection of MM cells compared with wild-type mice. Growth of the immunogenic MM cells was significantly reduced in S100A9KO mice. This effect was associated with the accumulation of Ag-specific CD8+ T cells in BM and spleens of S100A9KO mice, but not wild-type mice, and was abrogated by the administration of anti-CD8 Ab or adoptive transfer of MDSC. Thus, the accumulation of MDSC at early stages of MM plays a critical role in MM progression and suggests that MDSC can be considered a possible therapeutic target in this disease.

    • "Moreover, although the immune system in general suppresses multiple myeloma [72], not all immune cells mediate this role. Regulatory T-cells and immunosuppressive myeloidderived suppressor cells [73] are now being identified as important new targets that inhibit the immune response in multiple myeloma [74]. Interestingly, cellular immunity was found to be decreased in myeloma patients, including decreased ratio of CD4 "
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