Characteristics of the functional state of peripheral blood neutrophils in patients with luminal breast cancer

BACKGROUND: Neutrophils are essential in tumor growth, and their functional state can serve as a prognostic biomarker. However, the functional characteristics of peripheral blood neutrophils, such as chemotaxis and predisposition to NETosis, in female patients with luminal breast cancer have not been sufficiently explored. Studying these parameters may provide new insights into the mechanisms of disease progression and response to therapy. AIM: This work aimed to analyze the chemotactic activity of neutrophils and predisposition to NETosis in blood samples of female patients with locally advanced luminal breast cancer undergoing treatment (neoadjuvant chemotherapy) at the Loginov Moscow Clinical Scientific Center. METHODS: The study was conducted on blood samples from six patients with stage 3 luminal B, HER2-negative breast cancer before and 2 months after the start of antitumor therapy. Blood samples from healthy adult volunteers were used as controls. The work was performed using fluorescence microscopy methods for neutrophil chemotaxis with the growth of blood clots and the number of extracellular DNA traps of neutrophils by reaction with Hoechst 33342 and antibodies against myeloperoxidase and neutrophil elastase in smears of blood plasma rich in leukocytes. RESULTS: Before the start of neoadjuvant therapy, the level of NETosis is significantly increased (30% ± 14% versus 4.6% ± 3.4% in healthy donors), whereas most female patients undergoing therapy experience its reduction (17% ± 17%). The speed of neutrophil movement is increased in some female patients (0.17 ± 0.06 versus 0.113 ± 0.009 μm/s in healthy donors) and goes down during therapy (0.10 ± 0.03 μm/s). At the same time, the number of neutrophils associated with blood clots decreases during therapy (25 ± 18 versus 61 ± 23) even in patients with neutrophilia. CONCLUSION: It has been demonstrated for the first time that in female patients with luminal B, HER2-negative breast cancer, the neutrophil chemotaxis speed deviates from the standard; at the same time, their adhesion is reduced, and peripheral blood neutrophils are significantly more predisposed to NETosis than in healthy donors.