Decoding melanoma-immune cell communication through spatially resolved ligand-receptor interaction analyses

Abstract Melanoma is a highly immunogenic tumor where interactions between tumor and immune cells critically influence disease progression and treatment response. Traditional single-cell transcriptomics lack spatial context, limiting the understanding of these interactions within the tumor microenvironment. Here we integrated 10x Genomics Visium and Visium HD spatial transcriptomics with multiple single-cell RNA-seq datasets to map ligand-receptor interactions at the tumor-immune border region. This approach identified immune cell interactions already known in melanoma and highlighted unknown but prominent LGALS1 – PTPRC (proteins: galectin-1–CD45) interactions localized at the tumor-immune border region. Immunofluorescence and biolayer interferometry confirmed galectin-1 expression on melanoma cells and its binding to CD45 on infiltrating T cells. High LGALS1 expression correlated with reduced overall survival in patients undergoing checkpoint inhibitor therapy. These findings suggest that galectin-1–CD45 interactions contribute to immune modulation in melanoma and represent potential targets for immunotherapeutic strategies.