Malignant Melanoma-Associated Vitiligo
Malignant melanoma is a type of skin cancer resulted from uncontrolled growth of melanocytes. Although the exact mechanism implicated in the pathogenesis of malignant melanoma-associated vitiligo is still unclear, the immune reactivity against malignant melanoma cells, especially CD8+ T cells, is thought to play a critical role in vitiligo development [156, 157]. Malignant melanoma-associated vitiligo may arise from immune response directed against malignant melanoma-associated antigens expressed by both melanocytes and malignant melanoma cells. Indeed, antibodies reactive to tyrosinase [158], TYRP1, dopachrome tautomerase and Pmel17 [159] have been found in some malignant melanoma patient sera. Malignant melanoma studies showed that these melanocyte specific-antigens were recognised by self-reactive CD8+ T cells [160]. Following immunotherapy for metastatic malignant melanoma, enhanced efficacy is associated with CD8+ T cells. Immunotherapy for malignant melanoma involves blocking T-cell checkpoint inhibitors, which interfere with T cell tolerance in tissues, and adoptive cell therapy, which expands T cells that infiltrate autologous tumor ex vivo for therapeutic reinjection into melanoma patients [39]. Importantly, tumour infiltration with CD8+ T cells is vital in the effectiveness of both strategies [161], and these cells are thought to regulate malignant melanoma via perforin-dependent cytolysis [145]. New-onset vitiligo is commonly triggered by malignant melanoma therapy, and this occurs in about 4% such patients who are treated with immunotherapy [162]. Notably, vitiligo patches initiated by malignant melanoma immunotherapy are packed with CD8+ T cells that are specific to melanocytes, similar to idiopathic vitiligo patches [163]. Thus, CD8+ T cells are crucial to both the eradication of malignant melanoma and the pathogenesis of vitiligo. Therefore, the immune response in malignant melanoma patients which causes melanocyte damage is suggested to be cell-mediated, driven by CD8+ T cells and not by a humoral response. Thus, CD8+ T cells are crucial to both the eradication of malignant melanoma and the pathogenesis of vitiligo. Melanocyte-specific antibodies in malignant melanoma patients are likely to arise as a secondary immune response after melanocyte destruction via cell-mediated effects. Furthermore, the serum titres of malignant melanoma-related antibodies are low and their levels do not differ in patients with and without malignant melanoma-associated vitiligo. Vitiligo-like lesions in malignant melanoma patients receiving immunotherapy are considered as a good prognostic factor and have been correlated with a longer survival in these patients [164]. Development of vitiligo during treatment of malignant melanoma can be used as a clinical indication to predict and maintain the response [164].