Bacteria Colonization is Associated with Inflammation-Antigen Presentation Imbalance in Myeloid Cells and Tumor...

Intracellular microbes have been detected in multiple tumors, but their impact on the tumor microenvironment of melanoma and immune regulation remains unclear.

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.

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.

Intracellular colonizing bacteria were associated with inflammation-antigen presentation imbalance in melanoma tumor microenvironment.