Cytokine-producing function of circulating neutrophils during renal carcinogenesis: a case–control study

BACKGROUND: Cytokines produced by neutrophils may determine their pro- or antitumor activity, thereby contributing either to inhibition or progression of the tumor process. AIM: This work aimed to evaluate the cytokine-producing function of circulating neutrophils during renal carcinogenesis. METHODS: Circulating neutrophils were studied in patients with histologically verified early-stage renal cancer (stage I, n = 30) and advanced-stage disease (stage III, n = 30), as well as in conditionally healthy donors (control group, n = 30). Concentrations of monocyte chemoattractant protein-1 (MCP-1) and interleukin-2 (IL-2) (pg/mL) in neutrophil supernatants were determined by enzyme-linked immunosorbent assay. Gene expression of MCP-1 and IL-2 in neutrophils was assessed using quantitative polymerase chain reaction. Data are presented as median (Me) and interquartile range (Q1–Q3). Statistical analysis was performed using Statistica 13 and Jamovi 2.3.28. Differences were assessed using the Mann–Whitney U test (p 0.05). Correlation analysis was performed using the Spearman coefficient. Event probability was evaluated by odds ratio with 95% confidence intervals. A differential diagnostic model was constructed using binary logistic regression. Sensitivity and specificity were assessed by ROC curve analysis within the regression model. Predictive model performance was evaluated using the area under the ROC curve (AUC). RESULTS: A significant decrease in MCP-1 levels in neutrophil supernatants after 30 and 60 minutes of incubation was observed at stage III renal cancer compared with stage I, confirmed by an inverse correlation between MCP-1 levels and disease stage (r = −0.456; p = 0.015). At stage I renal cancer, IL-2 levels increased significantly after 30 minutes of incubation compared with controls under both spontaneous (p = 0.007) and induced conditions (p = 0.001). IL-2 gene expression and IL-2 production in neutrophils increased with renal cancer progression (p = 0.01). A direct correlation was observed between IL-2 gene expression in neutrophils and disease stage (r = 0.671; p = 0.001). In univariate logistic regression analysis, IL-2 gene expression in neutrophils demonstrated statistical significance for differentiation between early and advanced renal cancer stages (OR 0.156; 95% CI 0.047–0.525; p = 0.003). The model AUC was 0.932 (sensitivity, 0.938; specificity, 0.750). With renal cancer progression, IL-2 gene expression increased (R2 = 0.504; χ2 = 38.5; p = 0.001). CONCLUSION: At the early stage of renal cancer, neutrophils exert their antitumor potential via enhanced MCP-1 secretion. During renal cancer progression, increased IL-2 secretion confers protumor properties on circulating neutrophils.