Abstract
BACKGROUND: Cervical cancer (CC) is a major global health issue, ranking sixth in cancer-related mortality. The tumor microenvironment (TME) plays a crucial role in tumor growth. This study explored the cellular composition and immunological landscape of CC using various genomic data sources. METHODS: Data from the Cancer Genome Atlas and Gene Expression Omnibus were analyzed, including single-cell RNA sequencing, spatial transcriptome analysis, and survival data. Gene set variation analysis (GSVA) identified pathways in CD8+ cells, macrophages, and epithelial cells. Immunohistochemistry assessed marker expression in CC and normal tissues. Tumor immune dysfunction and exclusion (TIDE) scores differentiated high- and low-macrophage groups. Cell-cell communication analyses highlighted interactions between macrophages and epithelial cells. RESULTS: Macrophage markers correlated with overall survival (OS) and disease-free survival (DFS). Epithelial cell subgroups 1 and 4, along with CD8+ T cells, were associated with OS. TIDE scores varied between groups. Specific ligand-receptor interactions were found between macrophages and epithelial cell subgroup 1. Triptolide was effective in epithelial cell subgroup 1, while memantine was more effective in macrophages. CONCLUSION: Epithelial-macrophage interactions in the TME are crucial for CC progression and treatment, offering a potential immunotherapeutic strategy.