Immunohistochemical Profiling of IDO1 and IL4I1 in Head and Neck Squamous Cell Carcinoma: Interplay for Metabolic Reprogramming?

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and malignant disease with a limited number of biomarkers and insufficient targeted therapies. The current therapeutic landscape is challenged by low response rates, underscoring the need for new therapeutic targets. The success of immunotherapy in HNSCC has highlighted the importance of the immune microenvironment, and since metabolic reprogramming, especially altered tryptophan metabolism, is an important aspect in immune evasion, the interplay of the two enzymes IDO1 and IL4I1 was investigated in HNSCC to assess their immunosuppressive roles and potential as prognostic biomarkers. The immunohistochemical expression of IDO1 and IL4I1 was evaluated by an experienced head and neck pathologist in a tissue microarray (TMA) of 402 patients with HNSCC. Clinical and pathological data were retrieved, and the overall survival of the patients was calculated. In this study, IDO1 and IL4I1 were expressed by HNSCC tumor cells in the TMA of 402 patients. The overall survival analysis of the clinical data of the patients revealed that high IL4I1 expression was significantly associated with worse OS (<i>p</i> = 0.0073), while IDO1 expression did not reach statistical significance (<i>p</i> = 0.087). The combination of both markers led to a clinically significant stratification of patients. Especially p16-negative OPSCC with a high IL4I1 expression demonstrated poor survival. Immunologic differences between IDO1 and IL4I1 were detected in a TMA of 403 patients, with IDO1 and IL4I1 being expressed by HNSCC. A low IL4I1 expression in HNSCC led to a significantly better OS in this study, while IDO1 expression did not have a significant effect. Additional studies are necessary to investigate the complex interplay in the metabolic reprogramming of tumor cells.