Clinical and prognostic significance of sPD-1 and sPD-L1 in ovarian cancer

• Nikolay E. Kushlinskii
• Olga V. Kovaleva
• Alexey N. Grachev
• Dmitry A. Tsekatunov
• Dmitry N. Kushlinskiy
• Alexander A. Alferov
• Yurii B. Kuzmin
• Arina D. Shvedova
• Igor A. Klimanov
• Ivan S. Stilidi

Abstract

Introduction. Ovarian cancer is considered one of the most aggressive gynecological malignancies. Unfortunately, the methods that are currently considered the gold standard for the treatment of ovarian cancer, in most cases, lead to frequent relapses and progression of the disease after a limited period of time. Since the prognosis of this disease is often associated with the infiltration of the tumor by immune cells, immune checkpoint inhibitors can be used to activate the antitumor immune response in the treatment of tumors of this type. However, to date there is insufficient data to effectively select patients who can fully respond to this therapy.

The aim of the study is to study the level of soluble forms of PD-1 and PD-L1 (sPD-1 and sPD-L1) in ovarian tumors, their clinical and prognostic significance.

Material and methods. The study included 136 patients and 35 healthy women who were treated at the N.N. Blokhin NMRC of Oncology, MOH of Russia. The clinical diagnosis in all patients was confirmed by morphological examination of the tumor according to the International Histological Classification of Ovarian Tumors, adopted by WHO in 2014. The study included patients with epithelial ovarian cancer of three histological types: serous (77), endometrioid (13) and mucinous (8); benign neoplasms (22) and borderline tumors (10) of the ovaries, as well as non-epithelial ovarian tumors: dysgerminoma (3), sertolioma (1) and granulosa cell tumor (2). The levels of sPD-L1 and sPD-1 proteins was determined in blood plasma obtained according to standard methods before the start of specific treatment using an enzyme-linked immunosorbent assay. Statistical analysis of the obtained results was carried out using GraphPad Prizm v. 10. When comparing indicators and analyzing their relationships, nonparametric Mann–Whitney and Kruskal–Wallis tests and Spearman’s rank correlation coefficient were used. Overall survival analysis was performed by constructing survival curves using the Kaplan–Meier method. Differences were considered statistically significant at p < 0.05.

Results. The study showed that the median level of sPD-1 in the blood plasma of healthy women in the group of comparison was 43.8 (33.6–54.6) pg/ml, and in the group of patients with ovarian cancer – 47.1 (35.1–61. 6) pg/ml. The median level of sPD-L1 in blood plasma in the group of comparison was 60.8 (26.2–91.7) pg/ml and was not significantly higher than in patients with ovarian cancer 40.5 (15.7–78) pg/ml (p = 0.075). The level of sPD-L1 in blood plasma was significantly reduced in benign and non-epithelial malignant ovarian tumors (p = 0.022 and p = 0.006, respectively) compared to the group of comparison. It should be noted that the level of sPD-L1 in patients with nonepithelial ovarian tumors was significantly lower compared to epithelial tumors (p = 0.02). For sPD-L1 level, there is a significant association with tumor progression factors. Thus, the level of sPD-L1 is significantly higher in the later stages of the disease, in the case of larger tumors, in the presence of ascites and regional metastases. The analysis of prognostic significance showed that a high level of sPD-L1 protein in the plasma of patients with malignant ovarian tumors is a significant unfavorable prognostic factor (HR = 2.28; p = 0.023).

Conclusion. The study showed that the level of sPD-L1 in the blood plasma of patients with ovarian tumors reflects the extent of the tumor process and can potentially be an effective tool for monitoring the course of this disease. Also, our results and literature data indicate the prospects of using sPD-L1 level as a marker of the effectiveness of OC therapy, and therefore the prognosis of the disease.

Keywords:ovarian cancer; sPD-1; sPD-L1; prognosis

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