Morphofunctional state of neutrophils and cytokine status in patients with ovarian cancer

Abstract

Tatyana Vladimirovna Abakumova, Inna Ivanovna Antoneeva, Tatyana Petrovna Gening, Dinara Rishatovna Dolgova, Snezhanna Olegovna Gening

Introduction: The purpose of this study was to evaluate the morphofunctional state of polymorphonuclear neutrophils (PMN) and cytokine levels in the lysate of blood neutrophils of ovarian cancer (OC) patients. Methods: The absolute and the relative number of peripheral blood PMN in 120 primary OC patients (III-IV clinical stage FIGO) and 80 healthy women were determined. The expression of CD11a, 11b, 15 and CD95 in PMN was assessed by fluorescent microscopy. Cytochemically the myeloperoxidase (MPO) activity, the content of cationic proteins (CP), the activity in the spontaneous nitroblue tetrazolium (NBT)-test and phagocytic activity in PMN was determined. The amounts of cytokines tumor necrosis factors (TNF-α), interleukin (IL-1β), 1Ra, 6, 18, and granulocyte colony-stimulating factor (G-CSF) in serum were measured by the enzyme immunoassay method. Rigidity and topology of native PMN were assessed by scanning probe microscopy. To detect the differences between the data obtained in the evaluation of OC patients and healthy people, a non-parametric U-Mann–Whitney test was used. Reliable difference was considered at P ≤ 0.05. Results: These studies found an increase of the total number of PMN in peripheral blood, while reducing their cytotoxicity parameters. We observed reduced MPO activity and level of CP. Reducing in the levels of CD15 and CD95 expression on the background of increasing PMN activity in the spontaneous NBT-test may indicate a decrease in ability to complete phagocytosis. The dynamics of CD11a and CD11b expression in PMN was multidirectional, and the changes were not statistically significant. Polymorphonuclear neutrophils membrane stiffness decreased in Stage IV OC. We also observed the levels of IL-1β reduced up to 248.5 ± 9.00 pg/ml in Stage III OC, up to 230.9 ± 15.04 pg/ml in Stage IV OC versus 36.8 ± 10.74 pg/ml in control, reduced levels of 1Ra, and IL-18. We found that the level of IL-6 increased at Stage III OC up to 34.38 ± 9.74 pg/ml versus 7.66 ± 2.28 pg/ml in control and the levels of TNF-α and G-CSF decreased. Conclusion: Thus, these results suggest a state of secondary immunodeficiency in patients with OC at III-IV clinical stages of the disease.