CD14 + DCs present in the dermis of human skin represent a large subset of dermal DCs (dDCs) that are considered macrophage-like cells with poor antigen (cross)presenting capacity and limited migratory potential to the lymph nodes. CD14 + dDC highly express DC-SIGN, a receptor containing potent endocytic capacity, facilitating intracellular routing of antigens to MHC-I and -II loading compartments for the presentation to antigen-specific CD8 + and CD4 + T cells. Here we show using a human skin

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... xplant model that the in situ targeting of antigens to DC-SIGN using glycanmodified liposomes enhances the antigen cross-presenting capacity of CD14 + dDCs. Intradermal vaccination of liposomes modified with the DC-SIGN-targeting glycan Lewis X , containing melanoma antigens (MART-1 or Gp100), accumulated in CD14 + dDCs and resulted in enhanced Gp100-or MART-1 -specific CD8 + T cell responses. Simultaneous intradermal injection of the cytokines GM-CSF and IL-4 as adjuvant enhanced the migration of the skin DCs and increased the expression of DC-SIGN on the CD14 + and CD1a + dDCs. These data demonstrate that human CD14 + dDCs exhibit potent cross-presenting capacity when targeted in situ through DC-SIGN.