title: Vaccine-specific local T cell reactivity in immunotherapy-associated vitiligo in melanoma patients.
abstract: The occurrence of vitiligo in patients with melanoma is especially reported for patients undergoing immunotherapy. While vitiligo in these patients is thought to be related to an immune response directed against melanoma cells, solid evidence is lacking. Here we report local cytotoxic T cell reactivity in three melanoma patients who developed vitiligo, after experimental immunotherapy using dendritic cell vaccinations. Tetramer analysis showed that vaccine-induced T cells recognizing gp100 and tyrosinase are present at the vitiligo lesions. These T cells secrete IFN-gamma and IL-2 upon peptide specific stimulation as well as upon recognition of the autologous tumor. We show that functional CD8(+) T cells specific for melanoma differentiation antigens used in a melanoma immunotherapy trial, do not only invade the tumor, but also the vitiligo lesions. This directly links vitiligo to the immuno-therapeutic intervention and supports the hypothesis that vitiligo is a marker of immunity against melanoma cells.
authors.affiliation: Department of Pediatric Hemato-oncology, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
authors.forename: Joannes F M
authors.initials: JF
authors.lastname: Jacobs
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: Lenny A G
authors.initials: LA
authors.lastname: Sibelt
authors.forename: Willeke A
authors.initials: WA
authors.lastname: Blokx
authors.forename: Anna C I
authors.initials: AC
authors.lastname: Boullart
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Gerritsen
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hoogerbrugge
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
mesh_terms: D000368:Aged; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014820:Vitiligo / Q000209:etiology / Q000276:immunology*; D055815:Young Adult
chemical_list: D007371:Interferon-gamma