Tumor-Associated Macrophages and Regulatory T Cells as Predictors of Recurrence in Endometrial Stromal Tumors
DOI:
https://doi.org/10.52340/GBMN.2026.01.01.159Keywords:
CD163, disease-free survival, endometrial stromal sarcoma, FOXP3, regulatory T cells, tumor-associated macrophages, tumor microenvironmentAbstract
Background: Endometrial stromal tumors (EST) comprise a rare and biologically heterogeneous group of uterine mesenchymal neoplasms. While histological classification remains the primary prognostic determinant, recurrence patterns are not fully explained by tumor grade alone. The prognostic significance of immunosuppressive components of the tumor microenvironment in EST remains insufficiently characterized. Objectives: To evaluate the relationship between CD163-positive tumor-associated macrophages, FOXP3-positive regulatory T cells, and disease-free survival in patients with endometrial stromal tumors. Methods: This retrospective multicenter study included 90 patients diagnosed with endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), or high-grade endometrial stromal sarcoma (HG-ESS) between 2017 and 2025. Immunohistochemical expression of CD163 (tumor-associated macrophages) and FOXP3 (regulatory T cells) was quantified using digital image analysis. Disease-free survival (DFS) was evaluated using Kaplan–Meier estimates and Cox proportional hazards modeling. Results: Median follow-up was 55 months. Recurrence occurred in 34 patients (0 ESN, 12 LG-ESS, 22 HG-ESS). CD163 and FOXP3 densities increased significantly with histological grade (p<0.01). High CD163 and FOXP3 expression were independently associated with reduced DFS (Hazard Ratios 2.41 and 2.09, respectively; p<0.01). Tumors exhibiting concurrent high CD163 and FOXP3 infiltration demonstrated the poorest survival outcomes (HR 3.12, p<0.001), independent of grade. Conclusions: Enrichment of M2-polarized macrophages and regulatory T cells significantly influences the risk of recurrence in endometrial stromal tumors. Immune microenvironment profiling provides prognostic information beyond histological classification and may support future immunomodulatory therapeutic strategies.References
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