Systemic inflammation and tumor immune microenvironment biomarkers (FOXP3, CD68, CD163) stratified by BRCA/HRD status in high-grade serous ovarian carcinoma: Associations with PFS and OS.

Abstract

5546 Background: Outcomes in high-grade serous ovarian carcinoma (HGSOC) may be influenced by systemic inflammation and the tumor immune microenvironment. We evaluated the prognostic impact of systemic inflammatory markers and intratumoral immune biomarkers, including FOXP3⁺ regulatory T cells and tumor-associated macrophages (CD68 and CD163), in the context of BRCA/HRD status. Methods: We conducted a retrospective cohort study of patients with HGSOC with available baseline systemic inflammatory markers and tumor immunohistochemistry. Systemic inflammation was assessed using neutrophil-to-lymphocyte ratio (NLR >3.5) and lactate dehydrogenase (LDH >220). Intratumoral FOXP3, CD68, and CD163 expression was evaluated by immunohistochemistry. BRCA/HRD status was coded as positive versus negative. Progression-free survival (PFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. Results: Twenty-nine patients were included, with 27 PFS events and 25 OS events. In multivariable analysis for PFS, elevated systemic inflammation was independently associated with worse outcomes: NLR >3.5 (HR 5.88, 95% CI 1.35–25.54; p=0.018) and LDH >220 (HR 6.70, 95% CI 1.33–33.74; p=0.021). Within the tumor microenvironment, higher intratumoral CD68 was associated with inferior PFS (HR 1.10, 95% CI 1.04–1.17; p=0.001), whereas higher CD163 was associated with improved PFS (HR 0.92, 95% CI 0.87–0.97; p=0.002). BRCA/HRD positivity was not independently associated with PFS. For OS, BRCA/HRD positivity was strongly protective (HR 0.14, 95% CI 0.03–0.60; p=0.008), while NLR >3.5 remained independently associated with worse OS (HR 4.27, 95% CI 1.17–15.68; p=0.028). High FOXP3 expression was associated with improved OS (HR 0.06; p=0.032). CD68 and CD163 showed borderline associations with OS. Conclusions: In this HGSOC cohort, baseline systemic inflammation was associated with inferior PFS, and elevated NLR predicted worse OS. Intratumoral immune biomarkers showed distinct prognostic patterns, suggesting that the balance and functional state of myeloid and regulatory immune compartments influence outcomes. BRCA/HRD positivity remained strongly favorable for OS. These findings support further investigation of integrated systemic and tumor immune profiling in larger, prospectively annotated cohorts.