Elevated Plasma Interleukin-18 Levels in Head and Neck Squamous Cell Carcinoma: Correlation With IL-18 Binding Protein But Not Ferritin

Background/Aim: Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy of the upper aerodigestive tract, associated with poor survival. As part of the HNSCC microenvironment, the interleukin- 18 (IL-18)/IL-18 binding protein (IL-18BP) signaling is becoming increasingly interesting as a potential biomarker and therapeutic target. However, the systemic expression levels of IL-18BP in the context of the immunological environment in HNSCC patients remain unexplored. Materials and Methods: ELISA measurements of plasma IL-18-BP were carried out with regard to associated inflammatory markers such as C-reactive protein, acute phase protein ferritin, and IL-18 in 34 patients with HNSCC before and during the course of radio(chemo)therapeutic treatment and in correlation to the clinicopathological parameters. Results: Plasma IL-18BP concentrations were significantly elevated in HNSCC patients compared to healthy controls and correlated strongly with IL-18 levels before and after treatment. However, plasma ferritin levels, which were also elevated, showed no correlation with IL-18 or IL-18BP. Notably, changes in IL-18BP and IL-18 levels following therapy exhibited a well-maintained balance, indicating a functional feedback mechanism. Conclusion: The results demonstrate a robust IL-18/IL-18BP feedback regulation in HNSCC, which likely aids tumor cells in evading anti-tumor immune responses. This balance, unaffected by radiotherapy or chemoradiotherapy, underscores the potential of IL-18BP as a therapeutic target and a prognostic biomarker in HNSCC.