Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer

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.

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

“…Here, we found that, specifically, the IL6 high iCAFs co-occur with the stress-associated cancer cells, complementing a recent spatial transcriptomics study of pancreatic ductal adenocarcinoma ( 45 ). A chemoresistant role for TME-derived interleukin-6 (IL6) is further supported by findings where increased IL6 in peritoneal fluid ( 46 ), ascites ( 40 ), or blood plasma ( 47 ) associate with worse prognosis of patients with HGSOC. Ligand-receptor analysis suggests that paracrine signaling is amplifying the stress response by a feed-forward loop in both cancer cells and iCAFs.…”

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

“…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 ].…”

Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

“…All selected articles passed the STROBE checklist criteria (Supplementary Table S2). These include the articles of Sanna et al [35], Micheli et al [36], de Lima et al [37], Rodrigues et al [38], Kampan et al [25], Wertel et al [39], Zhang et al [40], Crispim et al [41], Shi et al [42], Li et al [43], Dalal et al [44], Han et al [45], Kumar et al [46], Martins-Filho et al [47], Cantón-Romeo et al [48], Sanguinette et al [49], Hao et al [50], Mikuła-Pietrasik et al [51], Chudecka-Głaz et al [ S1 and S2).…”