Localization of dendritic cells and T cells within the tumor microenvironment in different types of skin cancer

Abstract Immunophenotyping of tumor-infiltrating immune cells is increasingly important for understanding the tumor microenvironment (TME), particularly in the diagnosis and treatment of skin cancer. CD1a + dendritic cells (DC) initiate T cell activation by presenting tumor antigens, while T cells directly target tumor cells. Analyzing their spatial distribution in different types of skin cancer can provide insights into immune response patterns. To characterize the immune cell composition within the TME, we performed immunofluorescence staining for CD1a and CD3 on formalin-fixed, paraffin-embedded (FFPE) samples from actinic keratoses ( n = 18), squamous cell carcinoma ( n = 23), basal cell carcinoma ( n = 19), and melanoma ( n = 22), with nevi ( n = 16) and healthy skin ( n = 9) as controls. Immune cells were quantified across four tumor compartments: intratumoral, tumor margin, intraepidermal, and intradermal. Both CD1a + DC and CD3 + T cells were detected across all tumor entities, displaying distinct spatial distribution patterns. DC were enriched intratumorally and within the epidermis, whereas T cells predominantly accumulated at the tumor margin (main effect of region, p < 0.001). Melanoma exhibited significantly fewer DC at the tumor margin while maintaining strong T cell infiltration. Overall, the immune architecture of skin tumors is highly compartmentalized, characterized by region-specific DC and T cell distributions. These findings underscore the relevance of spatial immune profiling for understanding immune escape mechanisms and informing immunotherapeutic strategies.