Proinflammatory cytokines and circulating tumor cells in ovarian cancer patients treated with platinum-containing chemotherapy

Abstract

Summary. Circulating tumor cells (CTCs) are a potential source of tumor progression. Systemic tumor-associated inflammation can influence the cancer prognosis both independently and by changing the characteristics of CTCs. Data on the role of proinflammatory cytokines and CTCs in the ovarian cancer (OC) chemosensitivity are few and contradictory. Aim of the study. To assess the IL-17A, IL-18 levels and the number of CTCs in primary patients with OC before treatment and after 3 courses of standard platinum-containing chemotherapy, and the possibility of using these cytokines as a marker of the presence of CTCs. Materials and methods. The study included 72 patients with OC. The comparison group included 16 patients with benign ovarian tumors, the control group included 20 healthy women. The number of CTCs (CD45-/EpCam+/CK+) was determined immunofluorometrically before and after 3 courses of chemotherapy. The content of cytokines was assessed by ELISA. Statistica 13.0, jamovi 1.6.5.0 were used for data processing. Results. The level of IL-17A in blood in the benign tumors group was increased in comparison with OC (р=0.012) and control (р=0.042). The content of IL-17A increased over time in the subgroup of adjuvant chemotherapy (р=0.017). During treatment, IL-17A was higher among patients with platinum-sensitive tumors than with non-sensitive ones (р=0.054). High levels of IL-18 before treatment were associated with the development of platinum-refractory relapse (р=0.014). IL-18 levels before (р=0.027) and during treatment (p=0.052) were lower in patients with cytoreductive surgery in first line of treatment. Progression-free survival (PFS) (p = 0.012) and overall survival (OS) (p = 0.030) were lower in the cluster with high IL-18 and pretreatment leukocyte counts than in the cluster with low scores. Higher quantity of the pretreatment CTCs was associated with longer PFS in a multivariate analysis (HR 0.82 95% CI 0.69–0.98, р=0.028). The number of CTCs before treatment greater than 5 was associated with a decrease in OS (HR 1.31, 95% CI 0.98–1.73, р=0.064). Conclusions. A high level of IL-17A in the blood during treatment is associated with more favorable clinical characteristics of OC, while a high level of IL-18 in the blood before treatment is associated with less favorable characteristics and a worse prognosis. The number of CTCs in patients with OC is not related to the blood levels of IL-17A and IL-18. A greater number of CTCs before treatment in OC is associated with an increase in PFS, but a decrease in overall survival.