598P Can circulating PD-L1 levels, age at diagnosis and peritoneal carcinomatosis act as survival predictors in patients with advanced high-grade serous ovarian cancer?

Abstract

High-grade serous ovarian cancer (HGSOC) is the most frequent subtype of epithelial ovarian cancer (OC) with the greater immunogenic potential due to the abundance of tumor-infiltrating immune cells which modulate the anticancer immune response. Cancer cells may evade immune surveillance, by activating immunomodulatory proteins such as programmed death protein (PD-1) and its ligand PD-L1, butyrophilin sub-family 3A/CD277 receptors (BTN3A), butyrophilin sub-family 2 member A1 (BTN2A1), and the B and T lymphocyte attenuator (BTLA). Our study aimed to assess whether circulating levels of different immunoregulatory proteins could be helpful for predicting survival of advanced HGSOC patients. The plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA concentrations were analyzed in 100 advanced HGSOC women prior surgery and starting therapy, using specific ELISA tests not yet commercially available. This investigation allowed, for each tested circulating biomarker, to discriminate advanced HGSOC patients based on long (≥30 months) versus short Progression-free Survival (PFS <30 months). Through specific cut-offs obtained by ROC analysis, we showed that high baseline concentrations of PD-L1 (>0.42 ng/mL), PD-1 (>2.48 ng/mL), BTN3A1 (>4.75 ng/mL), pan-BTN3As (>13.06 ng/mL), BTN2A1 (>5.59 ng/mL) and BTLA (>2.78 ng/mL) were associated with unfavorable prognosis and median PFS from 6 to 16 months shorter. Additionally, age at diagnosis >60 years, BMI>25 or peritoneal carcinomatosis were correlated with a lower PFS (<30 months). Finally, a multivariate analysis highlighted that plasma levels of PD-L1≤0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p=0.002), age at diagnosis ≤60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p=0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p=0.003) were significant prognostic factors for a longer PFS in advanced HGSOC women. Assessing circulating PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1 and BTLA levels could facilitate the identification of high-risk patients with unfavorable disease outcomes, suggesting their potential use as prognostic biomarkers.