title: Human melanoma cells inhibit the earliest differentiation steps of human Langerhans cell precursors but failed to affect the functional maturation of epidermal Langerhans cells.
abstract: Tumour-derived factors suppress differentiation and function of in vitro generated DC. Here, we investigate the effect of two melanoma clones differing in their invasive and metastatic properties on the generation and/or functional maturation of human epidermal LC. LC were generated from CD34(+) cord blood progenitors under GM-CSF/TNF-alpha/TGF-beta 1. CD34(+) cells were co-cultured with or without melanoma cells using Transwell dishes. After 11 days of co-culture, CD34(+)-derived cells display a non-adherent undifferentiated morphology, a high level of monocytic CD14 marker, a down-regulated expression of LC markers (CD1a, E-cadherin) and DC markers (CD40, CD80, CD54, CD58, CD83, CD86, HLA-DR, HLA-class I). These cells were less potent than control LC in inducing allogeneic T cell proliferation. The generation of the CD14(+) population was correlated with a decrease in the CD1a(+) population, without any statistical differences between the two clones. Melanoma cells diverted the differentiation of CD34(+) cells towards a dominant CD14(+) population only if the progenitors were in an early growth phase. IL-10, TGF-beta 1 and VEGF were not responsible for these effects, as assessed by using blocking antibodies. By contrast, co-culture of fresh epidermal LC with melanoma cells did not affect their phenotype and function. Our data demonstrate that melanoma cells inhibit the earliest steps of LC differentiation, but failed to affect the functional maturation of epidermal LC. This suggests that melanoma cells participate in their own escape from immunosurveillance by preventing LC generation in the local cutaneous microenvironment.
authors.affiliation: INSERM U 346, Hôpital Edouard Herriot, F-69437 Lyon, France.
authors.forename: O
authors.initials: O
authors.lastname: Berthier-Vergnes
authors.forename: M
authors.initials: M
authors.lastname: Gaucherand
authors.forename: J
authors.initials: J
authors.lastname: Péguet-Navarro
authors.forename: J
authors.initials: J
authors.lastname: Plouet
authors.forename: J F
authors.initials: JF
authors.lastname: Pageaux
authors.forename: D
authors.initials: D
authors.lastname: Schmitt
authors.forename: M J
authors.initials: MJ
authors.lastname: Staquet
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D018920:Coculture Techniques; D016228:Endothelial Growth Factors / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007157:Immunologic Surveillance; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008222:Lymphokines / Q000502:physiology; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D018950:Lipopolysaccharide Receptors; D008222:Lymphokines; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016753:Interleukin-10