Vitiligo and melanoma: The fine balance between autoimmunity and immune escape

Work over the past years has increased our understanding on the role of the immune system in the human pigment cell disorders vitiligo and melanoma. Yet, pathogenic mechanisms of vitiligo are still incompletely studied and immune evasion still occurs among immunotherapy-treated melanoma patients. The work described in this thesis therefore aimed to on the one hand investigate the role of the immune system in melanoma and vitiligo, and on the other hand study whether and, if so, how melanocytes and melanoma cells contribute to immune evasion. We demonstrate that a besides a localized cytotoxic reaction against epidermal melanocytes, a significant proportion of vitiligo patients also show systemic immune activation. In addition, melanocytes from vitiligo patients do not confer protection against the T cell attack by PD-L1 upregulation. This provides a rational to study the possibilities of immunosuppressive therapy in the treatment of vitiligo. In melanoma, tissue-resident memory T (TRM) have an important protective role in melanoma. Nonetheless, we show that TRM cells are not abundantly present in pre-cancerous tissues and suggests that T cell infiltration and TRM cell differentiation do not occur yet at the pre-malignant stage. Furthermore, we investigated melanoma heterogeneity to unravel the phenotype of tumor cells that are insufficiently targeted by current immunotherapies. Our findings contribute to a better understanding of autoimmunity in vitiligo and immune evasion in melanoma.