UV Exposure Boosts Transcutaneous Immunization and Improves Tumor Immunity: Cytotoxic T-Cell Priming through the Skin

Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application...

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Veröffentlicht in:Journal of investigative dermatology 2011-01, Vol.131 (1), p.211-219
Hauptverfasser: Stein, Pamela, Rechtsteiner, Gerd, Warger, Tobias, Bopp, Tobias, Fuhr, Thorsten, Prüfer, Steve, Probst, Hans-Christian, Stassen, Michael, Langguth, Peter, Schild, Hansjörg, Radsak, Markus P.
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Sprache:eng
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Zusammenfassung:Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application onto intact skin induces potent cytotoxic T lymphocyte (CTL) responses and protection against transplanted tumors. The purpose of this study was to explore the effects of UV irradiation on imiquimod-based TCI. Here we show that skin exposure to low-dose UV light before TCI with imiquimod strongly boosts specific CTL responses leading to memory formation and enhanced tumor protection. Toward the mechanisms, we show that the activation of bone-marrow-derived dermal dendritic cells (DCs), but not Langerin-expressing DCs, is responsible for enhanced CTL activation. We describe an optimized TCI method that mediates enhanced CTL and antitumor responses by a DC- and TLR-dependent mechanism. These data may provide the basis for the future development of advanced vaccination protocols against tumors and persistent virus infections.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2010.254