Abstract Vulvovaginal melanoma (VVM) is a rare malignancy with poor prognosis and limited evidence to guide immunotherapy selection. This study aimed to assess the expression and interrelationships of programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8), and their associations with clinicopathological features and outcomes. Fifteen VVM cases were analysed using immunohistochemistry. PD-L1 was evaluated using tumour proportion score (TPS), immune cell score (IS), and combined positive score (CPS), CTLA-4, CD4, and CD8 were scored. Continuous marker values were analysed using Pearson correlation, with additional descriptive and spatial assessment of marker distribution . Survival and treatment data were reviewed when available. Most tumours showed high expression of PD-1, PD-L1 (IS/CPS), CTLA-4, CD4, and CD8, whereas PD-L1 (TPS) was comparatively lower. Significant positive correlations were observed between PD-1 and CD8, PD-1 and PD-L1 (IS/CPS), CD8 and PD-L1 (CPS), and between CTLA-4 and PD-L1 (TPS/CPS), indicating coordinated immune-checkpoint activation. PD-L1 expression was frequently enriched at the tumour–stroma interface. High CD4 expression correlated with increased mitotic rate, while CD8 and CTLA-4 expression correlated with melanin status. Higher PD-1, PD-L1, and CTLA-4 expression generally associated with longer overall survival following immunotherapy. In a case with serial recurrences, PD-1, PD-L1 (TPS, CPS), CTLA-4 expression increased while PD-L1 (IS) and CD4 + /CD8 + ratio decreased, suggesting a progressively immunosuppressive tumour microenvironment. These findings suggest that integrated immune profiling of PD-1, PD-L1, CTLA-4, and T-cell subsets may serve as predictive markers for immunotherapy in VVM.
Li et al. (Sat,) studied this question.