Expression and prognostic value of PD-L1 and PD-L2 in ovarian cancer

Background: In the present study, we aimed to investigate the expression and prognostic value of co-stimulatory molecules, programmed death ligand-1 (PD-L1) and PD-L2, in ovarian cancer (OC). Methods: Immunohistochemical (IHC) staining was used to assess the expressions of PD-L1 and PD-L2 in 77 cases of OC, and 10 cases of benign ovarian cyst were employed as negative controls. Moreover, chi(2) test was used to analyze the correlation between the PD-L1/PD-L2 expression and clinicopathological parameters. Kaplan-Meier method was used to compare the effects of PD-L1/PD-L2 expression level on the overall survival (OS) of OC patients. Results: PD-L1 and PD-L2 were mainly expressed on membrane and in cytoplasm of OC cells. The high-expression rate of PD-L1 and PD-L2 in OC tissues was 44.16% (34/77) and 22.08% (17/77), respectively. The expression of PD-L1 in OC cells was significantly correlated with FIGO stage (P= 0.026), while its expression was not significantly correlated with other clinicopathological parameters. There was no significant correlation between PD-L2 and any clinicopathological parameters. Kaplan-Meier survival analysis showed that the OS of high PD-L1 expression group was significantly shorter compared with the low PD-L1 expression group (HR = 2.689, 95% CI: 1.400-5.163). Patients with high PD-L2 expression also exhibited significantly shorter OS (HR = 2.204, 95% CI: 1.037-4.682). Multivariable analysis displayed that high expression of PD-L1 (HR = 2.275, 95% CI: 1.120-4.169), high expression of PD-L2 (HR = 2.314, 95% CI: 1.136-4.714) and FIGO stage (HR = 11.229, 95% CI: 1.373-91.865) were independent prognostic factors of OC. When negative expressions of both PD-L1 and PD-L2 were used as a combined prognostic factor, the OS was significantly prolonged (HR = 3.396, 95% CI: 1.858-6.029). According to our previous studies, patients with negative PD-L1 expression and high T-bet(+) TIL infiltration have higher OS than other patients. Patients with positive PD-L1 expression and low T-bet(+) TIL infiltration exhibit the shortest OS. Collectively, our findings provided the basis for PD-1/PD-L1 or PD-1/PD-L2 blockade therapy for OC patients. Conclusions: Co-stimulatory molecules, PD-L1 and PD-L2, were highly expressed in OC tissues, and their expression levels were correlated with FIGO stage, age and prognosis. These results suggested that PDL1 and PD-L2 were involved in the occurrence and development of malignant OC, indicating their potential value in clinical diagnosis and prognosis of OC.