title: UV exposure boosts transcutaneous immunization and improves tumor immunity: cytotoxic T-cell priming through the skin.
abstract: 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.
authors.affiliation: Institute of Immunology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.forename: Gerd
authors.initials: G
authors.lastname: Rechtsteiner
authors.forename: Tobias
authors.initials: T
authors.lastname: Warger
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Thorsten
authors.initials: T
authors.lastname: Fuhr
authors.forename: Steve
authors.initials: S
authors.lastname: Prüfer
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Probst
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
mesh_terms: D000634:Aminoquinolines / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D000077271:Imiquimod; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000819:agonists; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000276:immunology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000528:radiation effects*; D051199:Toll-Like Receptor 7 / Q000819:agonists; D014466:Ultraviolet Rays
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000077271:Imiquimod