Tissue Factor Expression Is Associated with Distinct Pattern of Immune-Cell Infiltration in the Ovarian Tumor Microenvironment
- 1Department of Gynecology and Obstetrics, Medical Faculty, Justus-Liebig-University Giessen, Klinikstr. 33, 35392 Giessen, Germany
- 2Clinic for Gynecology and Obstetrics, University Hospital Brandenburg, Medizinische Hochschule Brandenburg, Hochstraße 29, 14770 Brandenburg an der Havel, Germany
- 3Institute of Biology, Martin Luther University, Weinbergweg 10, 06120 Halle, Germany
Abstract
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.
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BibTeX
@article{mohiuddin2026tissue,
title = {{Tissue Factor Expression Is Associated with Distinct Pattern of Immune-Cell Infiltration in the Ovarian Tumor Microenvironment}},
author = {T. M. Mohiuddin and Fatema Binte Hafiz and Wenjie Sheng and Chaoyu Zhang and Marwah Al-Rawe and Felix Zeppernick and Svetlana Tchaikovski and Ivo Meinhold-Heerlein and Ahmad Fawzi Hussain},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209148},
url = {https://www.mdpi.com/1422-0067/27/20/9148},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tissue Factor Expression Is Associated with Distinct Pattern of Immune-Cell Infiltration in the Ovarian Tumor Microenvironment
AU - T. M. Mohiuddin
AU - Fatema Binte Hafiz
AU - Wenjie Sheng
AU - Chaoyu Zhang
AU - Marwah Al-Rawe
AU - Felix Zeppernick
AU - Svetlana Tchaikovski
AU - Ivo Meinhold-Heerlein
AU - Ahmad Fawzi Hussain
PY - 2026
DA - 2026/10/15
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209148
UR - https://www.mdpi.com/1422-0067/27/20/9148
AB - 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.
SN - 1422-0067
ER -