Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients.
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.
Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, Mailstop C313, 12631 E. 17th Ave, Aurora, CO, 80045, USA.
Kimberly R
KR
Jordan
Rodabe N
RN
Amaria
Oscar
O
Ramirez
Eryn B
EB
Callihan
Dexiang
D
Gao
Michelle
M
Borakove
Elizabeth
E
Manthey
Virginia F
VF
Borges
Martin D
MD
McCarter
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D055815:Young Adult
D018950:Lipopolysaccharide Receptors