Increased frequencies of CD11b(+) CD33(+) CD14(+) HLA-DR(low) myeloid-derived suppressor cells are an early event in melanoma patients.
Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population characterized by immunosuppressive activity. Elevated levels of MDSC in peripheral blood are found in inflammatory diseases as well as in malignant tumors where they are supposed to be major contributors to mechanisms of tumor-associated tolerance. We investigated the frequency and function of MDSC in peripheral blood of melanoma patients and observed an accumulation of CD11b(+) CD33(+) CD14(+) HLA-DR(low) MDSC in all stages of disease (I-IV), including early stage I patients. Disease progression and enhanced tumor burden did not result in a further increase in frequencies or change in phenotype of MDSC. By investigation of specific MDSC-associated cytokines in patients' sera, we found an accumulation of IL-8 in all stages of disease. T-cell proliferation assays revealed that MDSC critically contribute to suppressed antigen-specific T-cell reactivity and thus might explain the frequently observed transient effects of immunotherapeutic strategies in melanoma patients.
Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Berenice M
BM
Rudolph
Carmen
C
Loquai
Alexander
A
Gerwe
Nicole
N
Bacher
Kerstin
K
Steinbrink
Stephan
S
Grabbe
Andrea
A
Tuettenberg
D039481:CD11b Antigen / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D022423:Myeloid Cells / Q000737:chemistry / Q000276:immunology*; D009367:Neoplasm Staging; D011948:Receptors, Antigen, T-Cell; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000032:analysis; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013745:Tetanus Toxoid / Q000494:pharmacology; D047368:Tumor Burden; D019139:Tumor Escape
D039481:CD11b Antigen; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D011948:Receptors, Antigen, T-Cell; D063268:Sialic Acid Binding Ig-like Lectin 3; D013745:Tetanus Toxoid
immune monitoring; immune tolerance; immunotherapy; malignant melanoma; myeloid-derived suppressor cells