Bacteria Colonization is Associated with Inflammation-Antigen Presentation Imbalance in Myeloid Cells and Tumor Microenvironment Features in Melanoma

BACKGROUND: Intracellular microbes have been detected in multiple tumors, but their impact on the tumor microenvironment of melanoma and immune regulation remains unclear. METHODS: We applied single-cell host-microbe interaction analysis to single cell RNA sequencing data from 42 melanoma samples to characterize host-microbe interactions. Multiple functional annotation approaches were integrated to assess immune and tumor cell transcriptional states associated with bacteria colonization. RESULTS: Intracellular bacteria, particularly human-colonizing bacteria were associated with distinct transcriptional alterations in the tumor immune microenvironment, characterized by increased inflammation and reduced antigen presentation signatures in myeloid cells, along with enhanced innate immune-related transcriptional patterns, whereas adaptive T cell-related immune signatures were reduced. Tumor cells also exhibited transcriptional alterations, including increased metabolic activity and extracellular matrix remodeling pathways. At the bulk transcriptomic level, colonizing bacteria-associated chronic inflammatory features were correlated with increased CD8+ T cell infiltration and improved overall survival, while also showing a potential association with responses to immunotherapy. CONCLUSIONS: Intracellular colonizing bacteria were associated with inflammation-antigen presentation imbalance in melanoma tumor microenvironment.