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• W4387142337 abstract "<h3>Introduction/Background</h3> High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic cancer. This tumor spreads following peritoneal fluid (PF) dynamics, being the most representative biofluid of the tumor micro-environment (TME). In the TME, neutrophils can participate in cancer progression through neutrophil extracellular traps formation (NETosis). Evidence in murine OC models suggests that the primary tumor secrete specific cytokines (G-CSF, GROα, IL-8, MCP-1), triggering neutrophil recruitment and NETosis in the peritoneal cavity. Thus, we aimed to identify whether these NETosis-related cytokines are increased in the TME of HGSOC patients and to unravel their association with NETosis biomarkers. <h3>Methodology</h3> PF samples from advanced-HGSOC patients without neoadjuvant treatment (NT) (n=36), with NT (n=13), and control women (n=21) were analyzed. A simultaneous quantification of G-CSF, GROα, IL-1β, IL-6, IL-8, MCP-1, and TNFα was performed. Levels of NETosis biomarkers (cell-free DNA, nucleosomes, citrullinated histone 3, calprotectin, and myeloperoxidase) were quantified. R (v.3.6.2) was used for statistical analyses. <h3>Results</h3> Compared to control women, patients without NT presented a significantly higher concentration of GROα, IL-6, IL-8 and TNFα p≤0.004 (figure 1). In NT patients, the levels of the 4 cytokines decreased to those of controls. Considering patients without NT and control women, a positive correlation was observed among the 4 cytokines (Spearman-ρ≥0.389; p≤0.011) and between the cytokines and the 5 NETosis biomarkers (Spearman-ρ≥0.361; p≤0.039). <h3>Conclusion</h3> The observed increase of GROα, IL-6, IL-8 and TNFα levels in advanced-HGSOC patients’ PF demonstrate their presence in the HGSOC TME. Interestingly, NT decreased cytokines levels approaching to those of controls. The positive correlation described between the 4 cytokines and NETosis biomarkers suggest their possible involvement in triggering NETosis in the peritoneal cavity. Altogether, we found that GROα, IL-6, IL-8 and TNFα are present in HGSOC TME and could be involved in neutrophil recruitment and induction of NETosis, thus favoring HGSOC progression. <h3>Disclosures</h3> This research was funded by the ‘Instituto de Salud Carlos III Fondo Europeo de Desarrollo Regional’ (PI20/00075, PI22/01872) and the ‘Fundación para la Investigación del Hospital General Universitario de Valencia’ (FIHGUV Awards 2021). S. T.-P. is supported by pre-doctoral a grant from the ‘Junta Asociada Provincial de Valencia de la Asociación Española Contra el Cáncer (AECC)’; J. O. is supported by post-doctoral a grant from the ‘Alexander von Humboldt Foundation’; B. A. M.-C. is supported by a post-doctoral grant from the ‘Sociedad Española de Trombosis y Hemostasia (Prime SETH), R. H. is supported by a pre-doctoral grant from the ‘Instituto de Salud Carlos III’ (FI21/00171); E. G.-C., I. A.-C. and S. T.-M are supported by pre-doctoral grants from the ‘Generalitat Valenciana’ (ACIF/2020/216, ACIF/2021/192 and ACIF/2018/275, respectively). A. H.-P. is supported by a post-doctoral Marie Sklodowska-Curie grant (No. 101064216)." @default.
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• W4387142337 date "2023-09-01" @default.
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• W4387142337 title "#377 NETosis-related cytokines levels in the peritoneal fluid from advanced high-grade serous ovarian cancer patients" @default.
• W4387142337 doi "https://doi.org/10.1136/ijgc-2023-esgo.777" @default.
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