Immunophenotypic Features of T-Lymphocyte Distribution Across Histological and Molecular Subtypes of Serous Ovarian Neoplasms: A Retrospective Immunohistochemical Study

Background/Objectives: Serous ovarian neoplasms comprise biologically distinct entities with substantial differences in clinical behavior and molecular characteristics. Comparative data on the quantitative and spatial distribution of T-cell populations across the spectrum of serous ovarian neoplasms, particularly borderline ovarian tumors (BOT) and serous cystadenomas (CA), remain limited. The aim of this study was to compare the quantitative and spatial distribution of CD3+, CD4+, CD8+, and FOXP3+ cells across serous ovarian neoplasms and to assess their associations with selected molecular characteristics. Methods: This retrospective, single-center observational study included 227 patients with high-grade serous carcinoma (HGSC; n = 108), low-grade serous carcinoma (LGSC; n = 49), BOT (n = 16), and CA (n = 54). The primary endpoint was the density of CD3+, CD4+, CD8+ and FOXP3+ immunopositive cells per mm2, evaluated by immunohistochemistry and digital morphometry. Spatial distribution, differences across early pT substages, the CD8+/FOXP3+ ratio, and associations with selected molecular characteristics were additionally assessed. Age-adjusted generalized linear models were used to evaluate whether differences among histological groups were independent of patient age. Results: Compared with CA, HGSC showed an 18.58-fold higher CD3+ cell density and a 9.07-fold higher FOXP3+ cell density (both p < 0.001). Histological type remained significantly associated with CD3+, CD4+, CD8+, and FOXP3+ cell densities after adjustment for patient age (all p < 0.001), whereas age itself was not independently associated with any of the four markers (all p > 0.05). CD3+ cells were predominantly distributed in peritumoral areas, whereas HGSC also demonstrated diffuse intratumoral and stromal infiltration. Comparatively high T-cell densities were observed in BRCA1/2-mutated HGSC and HRD-positive subgroups. No statistically significant differences in immunopositive cell densities were detected across the analyzed pT1 substages. HGSC showed the lowest CD8+/FOXP3+ ratio (Me 1.18 [1.06–1.34]). Conclusions: Serous ovarian neoplasms demonstrate distinct histology-associated patterns of T-cell infiltration and spatial distribution, with additional heterogeneity across selected molecular subgroups. These differences remained evident after adjustment for patient age. Their functional and prognostic significance requires further validation using expanded immunophenotypic panels, multiplex approaches, and longitudinal clinical outcomes.