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. This evidence concerns the gene IDO1 and head and neck squamous cell carcinoma.