title: Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by tumour-conditioned media retain the capacity to mature and induce TH1 T-cell proliferation.
abstract: The tumour microenvironment down-modulates antigen-presentation by dendritic cells (DC), presumably due to inhibition of DC maturation. Here, we sought to examine (1) whether monocyte-derived cells cultivated with tumour-conditioned media under conditions that are conducive to DC generation (APCTCM) resemble immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are functionally defective. Four tumour cell lines expressing different cytokines were used to mimic different tumour microenvironments. As compared to iDC, DCims or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and CD4. These markers and a high phagocytic capacity were unique features of these cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR and CD25 were up-regulated to levels considerably higher than in DCIL10 and comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated. Activated APCTCM induced 50-60% of the proliferative response of DCims in the allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC elicited approximately 10%). Activated APCTCM induced secretion of almost equal amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1 differentiation. When mature DCims were exposed to TCM, their immunostimulatory function was not significantly altered. However, when TCM were added to the co-cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the TCM. In summary, APCTCM display special features but can mature into DCims-like cells.
authors.affiliation: Department of Dermatology, University Medical Centre Mannheim, Ruprecht Karls University of Heidelberg, Mannheim 68167, Germany. pat.metharom@medscape.com
authors.forename: P
authors.initials: P
authors.lastname: Metharom
authors.forename: F W
authors.initials: FW
authors.lastname: Velten
authors.forename: S
authors.initials: S
authors.lastname: Goerdt
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D058851:GPI-Linked Proteins; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D017077:Culture Media, Conditioned; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG