The current status and future direction of percutaneous peptide immunization against melanoma

Dendritic cell (DC)-based tumor immunotherapy is widely known to elicit protective anti-tumor immune responses, although the safety and effectiveness have yet to be thoroughly explored. We reported that a disruption in the stratum corneum barrier resulted in enhanced permeability and alterations in the skin immune system in such a way that epidermal Langerhans cells (LCs) functioned as vigorous antigen presenters for T helper (Th) cells and cytotoxic T lymphocytes (CTLs). In both human and murine models, topical application of melanoma-associated antigen peptides onto stratum corneum barrier-disrupted skin, specifically induced tumoricidal immune responses in vivo and in vitro accompanying an increased expression of MHC and co-stimulatory molecules on LCs. In addition, for reasons of simplicity, safety and effectiveness, percutaneous peptide application has demonstrated a certain degree of feasibility in clinical approach in patients with melanoma. In the future, resolution of some of the outstanding issues concerning the selection of the most effective adjuvants in combination with barrier disruption and depletion of regulatory T (Treg) cell-mediated immune suppression would appear as essential to improve percutaneous melanoma immunotherapy.