EXPLORING THE POTENTIAL CORRELATION BETWEEN NEUTROPHIL EXTRACELLULAR TRAPS AND PROGNOSIS IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA AND HODGKIN’S LYMPHOMA

Abstract

Introduction: Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin and granule proteins that are released from neutrophils in response to infection. NET-release also occurs and contributes to inflammation, organ dysfunction and thrombosis in patients with non-infectious inflammatory conditions, such as cancer. In several solid cancer types, NETs have been associated with poorer prognosis by facilitating tumour growth and metastasis. One study has associated NETs with tumour progression and poorer prognosis in diffuse large B-cell lymphoma (DLBCL), however the knowledge of the role of NETs in lymphoma is sparse. Here, NETs were measured in plasma from patients with DLBCL and Hodgkin’s lymphoma (HL), and correlated to blood counts and clinical outcome of the patients. Methods: Plasma samples from patients with DLBCL (n = 72) and HL (n = 54), diagnosed between 2010 and 2015, were obtained from the Swedish Uppsala Umeå Comprehensive Cancer Consortium (U-CAN) biobank. The lymphoma samples, as well as healthy controls (n = 11), were analysed using a commercial enzyme-linked immunosorbent assay (ELISA) targeting citrullinated histone 3 in complex with externalized DNA, a biomarker considered specific for NETs. Data collected from patient records, including routine blood counts at diagnosis, clinical background and disease outcome, was correlated to the obtained plasma concentrations of NETs. Results: DLBCL and HL patients showed significantly elevated concentrations of NETs in plasma compared to healthy controls (median concentrations 60.07, 65.24 and 5.366 ng/mL, p < 0.0001). In both DLBCL and HL, trends towards better overall survival (p = 0.3308 and 0.0534 respectively) and better progression free survival (p = 0.2777 and 0.1056) were seen for patients with concentrations of NETs above median. While there was no correlation between sex or age and NET levels in DLBCL patients, HL patients under the age of 50 years showed a significant correlation with higher levels of NETs (p = 0.0021). In both DLBCL and HL patients, plasma NET-levels showed a positive correlation with the neutrophil count in blood at diagnosis (p = 0.0087 and 0.0001 respectively). A neutrophil-lymphocyte ratio above 3.0, a known predictor of worse outcome in cancer patients, showed a trend towards being correlated with worse prognosis in DLBCL patients, but this was less evident for HL patients. Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, Hodgkin lymphoma No conflicts of interests pertinent to the abstract.