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    Poster Networking

    Hemostatic Systems in Cancer, Inflammation and Immunity

    Poster Networking Session

    PB0707 - Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Cancer is associated with systemic pathologies contributing to mortality, such as thrombosis and distant organ failure. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and impaired organ function, as well as in metastasis. Nevertheless, the role of NETs as disease promoters in these situations is still underexplored

    Aims: The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer

    Methods: We have used the spontaneous MMTV-PyMT mouse model for mammary carcinoma. DNase I was administered to resolve NETs. Serum samples from cancer patients with different malignant disorders and a sex- and age-matched control group were also included in the analysis. Cardiac and inflammatory biomarkers such as BNP, GDF-15, troponins, TNFa, IL1b and sTNFRs were analyzed by qPCR or by ELISA. Mouse cardiac histology was analyzed by regular and electron microscopy. Plasma levels of NETs, as well as thrombin-antithrombin complexes, were measured by ELISA

    Results: Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1

    Conclusion(s): Our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. We suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients