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* Malaghan Institute of Medical Research, Wellington, New Zealand;
Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria;
Centre d’Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale Unité 631, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6102, Universite de la Mediterrannee, Marseille, France; and
Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Queen’s University, Belfast, United Kingdom
A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8+ T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8+ T cells in the blood that produced IFN-
and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8+ T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by research grants from the Health Research Council and Cancer Society of New Zealand, the Wellington Medical Research Foundation, and the Genesis Oncology Trust. P.S. was supported by the Erwin Schroedinger Auslandsstipendium from the Austrian Science Fund (FWF-J2479), and C.H.T. by the Austrian Science Fund (FWF-L120). I.F.H. was supported by a Sir Charles Hercus Health Research Fellowship.
2 Address correspondence and reprint requests to Dr. Patrizia Stoitzner. Department of Dermatology, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail address: Patrizia.Stoitzner{at}i-med.ac.at
3 Abbreviations used in this paper: DC, dendritic cell; 
-GalCer, -galactosylceramide; CMTMR, chloromethyl-benzoyl-aminotetramethyl-rhodamine; DT, diphtheria toxin; DTR, DT receptor; EGFP, enhanced GFP; LC, Langerhans cell.
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