A Comparative Analysis Dissecting the Immune Landscape of Vitiligo and Melanoma from a single-cell Perspective: Two Sides of the Same Coin?

Background: Vitiligo and melanoma, while sharing overlapping immune responses and cellular environments, represent distinct dermatological conditions. A comprehensive comparison of the immune microenvironments in vitiligo and melanoma through detailed single-cell analysis has not yet been thoroughly defined.

Methods: Integrated single-cell RNA sequencing (scRNA-seq) data were obtained from healthy controls, vitiligo and melanoma patients. Comprehensive analyses including differential gene expression, enrichment analysis, regulatory network, pseudotime trajectory and cell-cell interaction were conducted to elucidate the roles of various cell subtypes and their interactions within the disease microenvironments.

Results: In vitiligo, melanocytes undergo stress-induced activation of multiple cell death pathways and immune activation, whereas in melanoma, they survive by suppressing death signals. The immune microenvironment of vitiligo is dominated by CD8 + T cells, characterized by IFN-γ-CXCL9/10-CXCR3 axis-mediated melanocyte elimination. Stressed fibroblasts and stressed keratinocytes amplify these pro-inflammatory signals. In contrast, the melanoma microenvironment is regulated by Tregs and cancer-associated fibroblasts, leading to impaired cytotoxic function of CD8 + T cells.

Conclusions: The divergent immune microenvironments of vitiligo and melanoma are characterized by immune activation versus immune evasion. These findings provide novel insights into potential therapeutic targets for both conditions.