Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients
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Myeloid-derived suppressor cells are increased in the peripheral blood of advanced-stage cancer patients; however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in melanoma patients. We characterized the frequency and suppressive function of multiple subsets of myeloid-derived suppressor cells in the peripheral blood of 34 patients with Stage IV melanoma, 20 patients with Stage I melanoma, and 15 healthy donors. The frequency of CD14+ MDSCs (Lin− CD11b+ HLA-DR− CD14+ CD33+) and CD14− MDSCs (Lin− CD11b+ HLA-DR− CD14− CD33+) was increased in the peripheral blood of Stage IV melanoma patients relative to healthy donors. The frequency of CD14+ and CD14− MDSCs correlated with each other and with the increased frequency of regulatory T cells, but not with classically defined monocytes. CD14− MDSCs isolated from the peripheral blood of Stage IV melanoma patients suppressed T cell activation more than those isolated from healthy donors, and the frequency of these cells correlated with disease progression and decreased overall survival. Our study provides the first evidence that the frequency of CD14− MDSCs negatively correlates with clinical outcomes in advanced-stage melanoma patients. These data indicate that suppressive MDSCs should be considered as targets for future immunotherapies.
KeywordsMyeloid-derived suppressor cells Immunotherapy Immunosuppression Melanoma
This work was supported by a University of Colorado Cancer Center Fellowship, the University of Colorado Cancer Center Support Grant (P30CA046934), the American Cancer Society 2012 Roaring Fork Valley Postdoctoral Research Award, and the Conner Family Foundation Grant. We would like to thank the laboratory members of Dr. Virginia Borges and Dr. Pepper Schedin for critical reviews of the data and Eric Spongberg for his technical support. We would also like to thank Dr. Sonali Jindal and Pat Bell for their assistance and histology expertise.
Conflict of interest
The authors declare no conflict of interest.
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