Tissue Factor Expression Is Associated with Distinct Pattern of Immune-Cell Infiltration in the Ovarian Tumor Microenvironment

Tissue factor (TF) has been implicated in tumor progression and immune regulation, but its cellular sources and relationship with immune infiltration in ovarian cancer remain incompletely defined. We integrated single-cell RNA sequencing (GSE232314), analyses of The Cancer Genome Atlas (TCGA) ovarian cancer cohort, and multiplex immunofluorescence in an independent 25-case tissue microarray (TMA). Single-cell analysis showed that TF expression was concentrated in tumor epithelial cells and a discrete endothelial subpopulation, with minimal expression in immune and other stromal compartments. In the TCGA cohort, TF expression was not significantly associated with tumor stage, grade, disease-free survival, or overall survival. In TF-stratified analyses, however, high CD8+ T cell infiltration was associated with improved survival in the low-TF expression subgroup (HR = 0.60) but with worse survival in the high-TF subgroup (HR = 1.72); high M1 macrophage infiltration was associated with improved survival only in the low-TF subgroup. TF expression correlated negatively with estimated CD8+ T cell, memory B cell, and M1 macrophage infiltration and positively with naïve B cell infiltration. In the TMA cohort, high-TF tumors showed significantly lower CD56+ NK-cell and CD68+ macrophage infiltration and a lower CD68/CD163 ratio. Together, these findings show cross-sectional associations between TF expression and reduced measured abundance of several antitumor immune populations and a stratum-dependent association between CD8+ T cell infiltration and survival. These associations were not fully concordant between the transcriptomic (TCGA) and protein-level (TMA) cohorts and require prospective, formally tested validation. TF warrants further investigation as a candidate immune-context biomarker in ovarian cancer.