Immunomodulatory mediators IL-33, soluble ST2, IL-10, IFN-γ in the serum of patients with oral potentially malignant disorders and oral squamous cell carcinoma

Background Interleukin-33 (IL-33) and its receptor Suppression of tumorigenicity 2 (ST2), along with IL-10 and IFN- γ , exert contrasting roles in tumor growth, immune evasion, and host defense. IL-33/ST2 signalling can either promote tumor progression or, in some contexts, enhance anti-tumor immunity. However, the role of serum IL-33 and soluble ST2 in Oral squamous cell carcinoma (OSCC) or its precursor, Oral potentially malignant disorders (OPMDs), remains largely unexplored. Aims To evaluate whether IL-33 and ST2, in conjunction with their interactions with IL-10 and IFN- γ , influence tumor dynamics in OSCC, as reflected in their serum levels. Materials and methods Ninety participants were enrolled in this cross-sectional observational study and divided into three groups: Healthy controls (HC) ( n = 30), OPMDs ( n = 30), and OSCC ( n = 30). Clinicopathological data were recorded, and 5 mL of venous blood was collected from each subject prior to treatment. Serum IL-33, soluble ST2, IL-10, and IFN- γ levels were quantified using ELISA. The data were analysed by applying the Kruskal–Wallis/Mann–Whitney U -tests, Receiver operating characteristics (ROC) curve analysis, DeLong's test and binomial logistic regression (BLR), with significance set at p 0.05. Results The analysis demonstrated a progressive and significant increase in IL-33, ST2, and IL-10 levels from HC to OPMDs to OSCC ( p 0.001 ). In contrast, IFN- γ levels exhibited a significant inverse trend, being highest in OPMDs, comparable in HC, and lowest in OSCC ( p 0.001 ). Immune mediators in OSCC showed significant associations with clinicopathological parameters, including tumor stage, depth of invasion, lymph nodal metastasis (LNM), tumor budding, and surgical margin status ( p 0.05). Serum IL-10 was the strongest positive predictor, effectively discriminating lymph node status (LNS). IL-33 and soluble ST2 showed positive trends toward predicting LNM with high classification accuracy. ROC analysis showed excellent discriminatory ability of all immunomodulatory mediators for distinguishing OSCC from OPMDs. Although soluble ST2 had the highest AUC, DeLong's test ( p = 0.592) showed no significant difference, indicating comparable diagnostic potential. BLR confirmed their diagnostic relevance, with elevated IL-33, soluble ST2, and IL-10 increasing the odds of OSCC, while higher IFN- γ reduced the risk. Conclusion The panel of immunomodulatory mediators analysed here reflects a biologically relevant shift toward pro-tumorigenic inflammation and immune evasion, underscoring their role as biomarkers of malignant progression. Collectively, these immunomodulatory mediators demonstrated strong diagnostic accuracy in differentiating OSCC from OPMDs and showed potential for risk stratification.