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 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.
Stein
Pamela
P
Institute of Immunology, Johannes Gutenberg University Medical Center, Mainz, Germany.
Rechtsteiner
Gerd
G
Warger
Tobias
T
Bopp
Tobias
T
Fuhr
Thorsten
T
Prüfer
Steve
S
Probst
Hans-Christian
HC
Stassen
Michael
M
Langguth
Peter
P
Schild
Hansjörg
H
Radsak
Markus P
MP
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
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000077271:Imiquimod