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

Publication date: Jul 03, 2025

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. 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. 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. 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.

Concepts Keywords
Cancer Cell-cell Interaction
Cxcr3 Immune Microenvironment
Fibroblasts Melanoma
Healthy Single-cell
Microenvironment Vitiligo

Semantics

Type Source Name
disease MESH Vitiligo
disease MESH Melanoma
pathway KEGG Melanoma
disease MESH death
disease MESH cancer

Original Article

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