Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation

被引:77
作者
van de Ven, Rieneke
van den Hout, Mari F. C. M. [2 ]
Lindenberg, Jelle J.
Sluijter, Berbel J. R. [3 ]
van Leeuwen, Paul A. M. [3 ]
Lougheed, Sinead M.
Meijer, Sybren [3 ]
van den Tol, M. Petrousjka [3 ]
Scheper, Rik J. [2 ]
de Gruijl, Tanja D. [1 ]
机构
[1] Vrije Univ Amsterdam Med Ctr, Div Immunotherapy, Dept Med Oncol, Canc Ctr Amsterdam, NL-1081 HV Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Canc Ctr Amsterdam, NL-1081 HV Amsterdam, Netherlands
[3] Vrije Univ Amsterdam Med Ctr, Dept Surg Oncol, Canc Ctr Amsterdam, NL-1081 HV Amsterdam, Netherlands
关键词
EPIDERMAL LANGERHANS CELLS; ANTIGEN-PRESENTING CELLS; MELANOMA PATIENTS; INDOLEAMINE 2,3-DIOXYGENASE; CROSS-PRESENTATION; IN-VIVO; CD8(+); TUMOR; EXPRESSION; IMMUNOTHERAPY;
D O I
10.1182/blood-2011-03-344838
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 representativeof 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(hl) dermal DCs with variable expression of langerin. Two other CD1a(-) LN-residing cDC subsets were characterized as CD14(-) BDCA3(hl)CD103(-) and CD14(+) BDCA3(io) CD103(+), respectively. Whereas the CD1(a+) 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 IFN gamma 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. (Blood. 2011;118(9):2502-2510)
引用
收藏
页码:2502 / 2510
页数:9
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