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.