PB1382 - NETosis-related cytokines levels in the peritoneal fluid from advanced high-grade serous ovarian cancer patients

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

ST

Sarai Tomás-Pérez

PhD candidate
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain

Presenting Author(s)

JO

Julia Oto

Postdoctoral researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain

Co-Author(s)

AC

Aitor Cuadros-Lozano

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia
Valencia, Comunidad Valenciana, Spain
BM

Bárbara Andrea Mc Cormack

Postdoctoral researcher
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
RH

Raquel Herranz

PhD candidate
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
EG

Eva González-Cantó

PhD candidate
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
CA

Cristina Aghababyan

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
MC

María Castaño

Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
AH

Alejandro Herreros-Pomares

Postdoctoral researcher
Gynaecological Oncology Laboratory, Department of Oncology, KU Leuven, Leuven
Leuven, Vlaams-Brabant, Belgium
AL

Antoni Llueca

Medical doctor
Department of Obstetrics and Gynecology, General University Hospital of Castellon
Castellón, Comunidad Valenciana, Spain
JM

Josep Marí-Alexandre

Postdoctoral researcher
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
Pilar Medina, PhD

Principal Investigator
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Health Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
JG

Juan Gilabert-Estellés

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain

Background: 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.

Aims: To identify whether these NETosis-related cytokines are increased in the TME of HGSOC patients and to unravel their association with NETosis biomarkers.

Methods: PF samples from advanced-HGSOC patients without neoadjuvant treatment (NT) (n=36), with NT (n=13), and control women (n=21) were analyzed. 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.

Results: Compared to controls, 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 controls, 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).

Conclusion(s): 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.

Funding: ISCIII (PI20/00075, PI22/01872; FI21/00171); FIHGUV 2021; AECC 2022; SETH 2021 and 2023; GV (ACIF/2020/216); Marie Sklodowska-Curie (No. 101064216).