Immunothrombosis, tumor progression and metastasis. Role of interleukin-8 and neutrophil extracellular traps
Authors:   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Slukhanchuk E.V. , Bitsadze V.O. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Solopova A.G. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Khizroeva J.Kh. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Shcherbakov D.V. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, F.E.Yagubova F.E.Yagubova ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, J.-Ch.Gris J.-Ch.Gris ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, I.Elalami I.Elalami ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Degtyareva N.D. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Lazarchuk A.V. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Gileva M.A. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Aslanova Z.D. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Tsibizova V.I. ,   Almazov National Medical Research Centre, Saint Petersburg, Russian Federation, Shkoda A.S. ,   Vorokhobov City Сlinical Hospital No 67, Moscow, Russian Federation, Makatsariya A.D. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Published: February 2024

Immunothrombosis, tumor progression and metastasis are inextricably linked. These close interactions are carried out by several actors. Neutrophils are considered as players in the antimicrobial host defense. Activated neutrophils release extracellular traps (NETs) involved in antimicrobial immune response and pathogenesis of various conditions including tumor growth. Neutrophils and interleukin-8 (IL-8) play a key role in the formation of NETs. Objective. To evaluate the interaction between NETs and IL-8, their contribution to the development of immunothrombosis and tumor progression in patients with reproductive system cancers and breast cancer of different stages. Patients and methods. This study included 77 patients with malignant tumors of the endometrium, ovaries, cervix, and breast, and 33 healthy controls. Concentrations of citrullinated histone H3 (citH3), human myeloperoxidase antigen (MPO:Ag), D-dimer, thrombin-antithrombin complexes (TAT), and IL-8 were assessed in all patients before surgical treatment or chemotherapy upon admission to the hospital. Results. It was shown that the concentration of NETosis markers was significantly higher in cancer patients compared to healthy controls, with an increase in indicators against the background of disease progression in stages. Naturally, markers of hemostatic activation were elevated in gynecologic cancer patients, also with increasing indicators against disease progression. The concentration of IL-8 was used as a marker of inflammation in this study, which was significantly elevated in cancer patients. The correlation analysis showed that IL-8 concentrations increased with increasing levels of NETosis markers, demonstrating maximum values at late stages of the disease, which indicates an important role of immunothrombosis in cancer progression and metastasis. Conclusion. The study showed that the concentrations of NETosis markers and IL-8 are elevated in cancer patients, and the degree of this elevation correlates with the stage of the disease. A possible mechanism is capturing of tumor cells by networks, their shielding from immune system, subsequent expression of IL-8 by tumor cells with further involvement of neutrophils and initiation of NETosis. Key words: neutrophil extracellular traps, interleukin-8, immunothrombosis, metastasis, tumor progression, neutrophils