Abstract
Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n = 78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p < 0.0001). Significantly higher (p < 0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n = 31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.
Highlights
The prognosis for ovarian cancer (OC) patients is extremely poor
It has been proved that OC is an immunogenic tumor which induces antitumor immune response found in different ovarian cancer microenvironments (TMEs), e.g., peripheral blood (PB), peritoneal fluid (PF), and tumor tissue (TT)
We examined the relationship between the levels of Interleukin 6 (IL-6) and the percentage of programmed death ligand 1 (PD-L1)/PD-L2 positive CD45+CD14+ inflammatory cells in three different OC microenvironments: peripheral blood (PB), peritoneal fluid (PF), and tumor tissue (TT) and their clinical and prognostic relevance in ovarian cancer patients
Summary
The prognosis for ovarian cancer (OC) patients is extremely poor. It has been proved that OC is an immunogenic tumor which induces antitumor immune response found in different ovarian cancer microenvironments (TMEs), e.g., peripheral blood (PB), peritoneal fluid (PF), and tumor tissue (TT). The response is reinforced by locally occurring immune cells that induce strong inflammation and immunosuppression in TMEs. The tumor microenvironment in which OC develops has been described to be enriched with a broad spectrum of proinflammatory chemokines (CCL2, CCL4, and CXCL10), cytokines (e.g., IL-6, IL-8, IL-10, and IL-12), and factors (TNF-α and TGF-β), which have been shown to influence clinical disease status and prognosis [7,8,9]. IL-6 is of particular importance, because it exerts a wide variety of biological functions, involved in the induction of inflammation and resultant carcinogenesis as well as immune suppression in patients with cancer [10, 11]
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