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Multiple myeloma induces the immunosuppressive capacity of distinct myeloid-derived suppressor cell subpopulations in the bone marrow.

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Multiple myeloma (MM) establishes an immunosuppressive environment in the bone marrow (BM), rendering patients more susceptible to infections and limiting the efficacy of immunotherapeutic approaches. However, the exact nature of the immunosuppressive mechanisms at work in multiple myeloma-diseased BM remain elusive. Here, we demonstrate that two independent syngeneic immunocompetent mouse 5TMM models influence the activation state of BM CD11bhighLy6Glow and CD11bhighLy6Ghigh populations, thereby enhancing their T-cell antiproliferative capacity as compared to their naive counterparts. In addition, MM tumor growth skews myelopoiesis in favor of the more suppressive CD11bhighLy6Glow myeloid-derived suppressor cell (MDSC) subset. 5TMM-induced Ly6Glow MDSCs secrete higher levels of nitric oxide (NO), contributing partially to their suppressive activity, while neither NO nor reactive oxygen species (ROS) are implicated in the suppression by the neutrophil lineage-committed CD11bhighLy6Ghigh cells. Finally, Ly6Glow MDSCs are heterogeneous and consist of Ly6ChighSSClow monocytes, Ly6CintSSClow myeloid cells in early stages of differentiation and Ly6CintSSChigh eosinophils. Monocytes are consistently the most suppressive subpopulation, although the other fractions can be potentially suppressive as well. Overall, our data identify distinct subsets of MDSCs as part of MM-induced T-cell suppression in the BM, suggesting the usefulness of MDSC-targeted therapies in this disease.
Tijdschrift: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
ISSN: 0887-6924
Issue: 11
Volume: 26
Pagina's: 2424-2428
Jaar van publicatie:2012
Trefwoorden:myeloma
Toegankelijkheid:Closed