title: Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation.
abstract: To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a(+) subsets were identified as most likely skin-derived CD11c(int) Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11c(hi) dermal DCs with variable expression of langerin. Two other CD1a(-) LN-residing cDC subsets were characterized as CD14(-)BDCA3(hi)CD103(-) and CD14(+)BDCA3(lo)CD103(+), respectively. Whereas the CD1a(+) skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a(-) cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.
authors.affiliation: Departments of Medical Oncology, VU University Medical Center/Cancer Center Amsterdam, De Boelelaan, Amsterdam, The Netherlands.
authors.forename: Rieneke
authors.initials: R
authors.lastname: van de Ven
authors.forename: Mari F C M
authors.initials: MF
authors.lastname: van den Hout
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Lindenberg
authors.forename: Berbel J R
authors.initials: BJ
authors.lastname: Sluijter
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Sinéad M
authors.initials: SM
authors.lastname: Lougheed
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: M Petrousjka
authors.initials: MP
authors.lastname: van den Tol
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000032:analysis; D007801:Langerhans Cells / Q000737:chemistry / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000032:analysis; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000601:surgery; D021701:Sentinel Lymph Node Biopsy; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology*; D018180:Thrombomodulin
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D000954:Antigens, Surface; D039521:CD11c Antigen; C419393:CD1a antigen; C121916:CD207 protein, human; D015820:Cadherins; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008222:Lymphokines; D037241:Mannose-Binding Lectins; C546931:THBD protein, human; D018180:Thrombomodulin; C091367:alpha E integrins