<p>Programmed Death-1 Receptor (PD-1) as a Potential Prognosis Biomarker for Ovarian Cancer Patients</p>

Abstract

Aim: Ovarian cancer (OC) is one of the most lethal gynecological malignancies. Recent studies suggest a crucial role of the PD-1/PD-L1 pathway in OC pathogenesis. Therefore, our study aimed at evaluation of the clinical importance of PD-1 expression in ovarian cancer patients. Patients and Methods: In this study, we investigated the role of PD-1 in OC patients (n=50) by analyzing its expression on CD4 + and CD8 + T cells in three OC environments: peripheral blood (PB), peritoneal fluid (PF), and tumor (TT) as well as soluble PD-1 (sPD-1) in plasma and PF in terms of their clinical and prognostic significance. T cells with PD-1 expression were analyzed using flow cytometry. The concentration of sPD-1 was determined with the use of ELISA. Our research demonstrated differences in PD-1 expression on CD4 + and CD8 + T cells in the OC environments. Results: We found an elevated level of CD4 + PD-1 + T cells in tumor and PF, compared to PB. Additionally, we found the highest percentage of CD8 + PD-1 + in tumor, compared to PB and PF. The levels of sPD-1 were higher (p<0.0001) in plasma than in PF. For the first time, we discovered that the higher level of CD4 + PD-1 + T cells in the circulation and the higher sPD-1 level in plasma predict poor survival of OC patients. Conclusion: We suggest that PD-1 could be a predictive biomarker for OC patients and successful immunotherapy.

Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients

“…In our previous study, we established the sPD-1 level in the plasma and PF of ovarian cancer patients and its correlations with clinical data and patient outcomes [ 26 ].…”

“…In our previous report, we found that OC patients with a lower soluble PD-1 level in the plasma, but not in PF ( p > 0.05), had beneficial 5-year survival than those with a higher sPD-1 concentration [ 26 ].…”

“…In our earlier study, we demonstrated a correlation between the level of sPD-1 in plasma and PF and the survival of OC patients. Our results indicate that a significantly lower concentration of sPD-1 in the plasma is associated with beneficial OS of OC patients [ 26 ]. In contrast, Elhang and co-workers demonstrated that a higher sPD-1 level is related to beneficial survival in a murine model of OC via reduction in immunosuppression.…”

“…The obtained cell suspensions were filtered through a mesh filter (70 mm; BD Biosciences), which was followed by density centrifugation at 700× g on a Gradisol L (AquaMedica, Poland) for 20 min at room temperature. Afterward, cells from the interphase were collected, washed twice in phosphate-buffered saline (PBS, PAA Laboratories GmbH, Austria), and resuspended in PBS [ 26 , 70 ].…”

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

“…An original study suggested that higher PD-1 level in the plasma could be a predictive biomarker and predicted poor survival of OC patients. 40 In addition, a recent study by Kim et al showed that PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were correlated with a better prognosis in SC. 41 Interestingly, our results showed a high PD-L1 expression in CCC, implying poor prognosis, supporting the analysis of PD-L1 expression in this specific histological subtype with a potential benefit of targeted therapy.…”