Skin-Depigmenting Agent Monobenzone Induces Potent T-Cell Autoimmunity toward Pigmented Cells by Tyrosinase Haptenation and Melanosome Autophagy

Jasper G. van den Boorn, Daisy I. Picavet, Paul F. van Swieten, Henk A. van Veen, Debby Konijnenberg, Peter A. van Veelen, Toni van Capel, Esther C. de Jong, Eric A. Reits, Jan W. Drijfhout, Jan D. Bos, Cornelis J. M. Melief, Rosalie M. Luiten

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103 Citations (Scopus)

Abstract

In this study, we report the previously unknown mechanism of inducing robust anti-melanoma immunity by the vitiligo-inducing compound monobenzone. We show monobenzone to increase melanocyte and melanoma cell immunogenicity by forming quinone-haptens to the tyrosinase protein and by inducing the release of tyrosinase-and melanoma antigen recognized by T cells-1 (MART-1)-containing CD63+ exosomes following melanosome oxidative stress induction. Monobenzone further augments the processing and shedding of melanocyte-differentiation antigens by inducing melanosome autophagy and enhanced tyrosinase ubiquitination, ultimately activating dendritic cells, which induced cytotoxic human melanoma-reactive T cells. These T cells effectively eradicate melanoma in vivo, as we have reported previously. Monobenzone thereby represents a promising and readily applicable compound for immunotherapy in melanoma patients
Original languageEnglish
Pages (from-to)1240-1251
JournalJournal of investigative dermatology
Volume131
Issue number6
DOIs
Publication statusPublished - 2011

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