title: DC maturation and function are not altered by melanoma-derived immunosuppressive soluble factors.
abstract: BACKGROUND
  Although melanoma can elicit robust tumor antigen-specific immune responses, advanced melanoma is associated with immune tolerance. We have previously described several mechanisms of melanoma-induced immunosuppression, including the skewing of the immune response towards a Th2 cytokine profile and the induction of regulatory T cells. Since dendritic cells (DCs) are potentially important players that can direct other cells of the immune system towards a cytotoxic, humoral, or regulatory phenotype, we hypothesized that melanoma-produced factors directly affect the maturation and function of DCs, influencing the nature and magnitude of the resulting immune response.
  
  
  METHODS
  To test this hypothesis, immature myeloid-derived DCs (mdDCs) were derived with cytokines from CD14+ peripheral blood mononuclear cells (PBMCs) and exposed to 20% melanoma-conditioned media (MCM). After 2 d, the expression of maturation markers and the function of these mdDCs, measured by cytokine production, the amount of endocytosis, expression of the inhibitory molecule indoleamine 2,3-dioxygenase (IDO), and the ability to stimulate T cells were determined.
  
  
  RESULTS
  We found that incubation with MCM did not inhibit the expression of maturation markers or IDO, the production of cytokines, the amount of antigen uptake, or the ability to induce T cell proliferation in mixed-lymphocyte reactions by mdDC.
  
  
  CONCLUSIONS
  These results suggest that the immunosuppressive effects of melanoma-produced factors are independent of directly measurable changes in mdDC function or maturation in vitro.
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Baumgartner
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Jordan
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Hu
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCarter
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D013491:Suppressor Factors, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D013491:Suppressor Factors, Immunologic