Killing potential of circulating neutrophils in renal tumors

Relevance. Currently, the study of the role of neutrophils in the development of renal cancer is of considerable interest. The study of the immunopathogenesis of renal cancer is determined by the need to use combined treatment with immunotherapy. It is known that neutrophils have both pro- and antitumor properties, which are associated with the level of surface receptors CD11b, CD16, CD63, CD66b and the killing activity of neutrophils. The aim of the study was to assess the killing potential of circulating neutrophils in renal tumors. Materials and Methods. The object of the study was circulating neutrophils of patients with verified renal cancer (n  =  74), patients with renal benign neoplasms (n  =  18) and conditionally healthy donors (n  =  22). The study of the phenotype of the isolated neutrophils was carried out by flow cytometry. Neutrophil extracellular traps were counted using the method by I.I. Dolgushin. Results and Discussion. Analysis of the percentage of neutrophil extracellular traps showed an increase in their number in the groups of patients with renal cancer, both stages I–II and III–IV, relative to the control group and the group of patients with renal benign neoplasms. An increase in the neutrophil trap index was found in the groups of patients with renal cancer stages I–II and III–IV relative to the control group and the group of patients with renal benign neoplasms. When assessing the phagocytic activity and the phagocytic activity index, a significant increase in these indicators was found in the groups of patients with renal cancer relative to the control group and the group of patients with renal benign neoplasms. A correlation was found between the percentage of neutrophil extracellular traps (r  =  0.438, p = 0.001), the phagocytic activity (r = 0.431, p = 0.001) and the phagocytic activity index (r = 0.507, p = 0.001) of neutrophils and the stage of renal cancer. A significant increase in the percentage of neutrophils expressing CD66b receptors was found both at the initial and widespread stages of renal cancer relative to the group with renal benign neoplasms and the control group. Multivariate Cox regression revealed an increase in the risk of renal cancer with an increase in CD66b expression, the neutrophil extracellular traps index, the phagocytic activity and the phagocytic activity index of circulating neutrophils (R2 = 0.728, χ² = 58.1, p = 0.001). For differential diagnostics between renal benign neoplasms and renal cancer, the percentage of CD66b+ neutrophils, the neutrophil extracellular traps index, the phagocytic activity of neutrophils and the phagocytic activity indexneutrophils demonstrated statistical significance together. The area under the curve (AUC) of the model was 0.983, and could be diagnosed with a probability of 94.3% (Spec. = 0.889, Sens. = 0.962). Conclusion. Thus, an increase in CD66b+ neutrophils and activation of extracellular trap release indicate an increase in the killing activity of neutrophils in renal cancer. Simultaneous determination of the amount of CD66b+ neutrophils, the index of neutrophil extracellular traps, phagocytic activity and the index of phagocytic activity can be used for differential diagnosis between the renal benign neoplasms and renal cancer.