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].