IL4I1 is a secreted L-amino-acid oxidase functioning as a key immunoregulator with preference for aromatic amino acids 1. It converts phenylalanine, tyrosine, and tryptophan to their respective pyruvic acid derivatives, with particular significance for tryptophan catabolism via an indole pyruvate pathway 12. IL4I1-mediated tryptophan degradation generates indole metabolites and kynurenic acid that activate the aryl hydrocarbon receptor (AHR), a transcription factor critical for immune regulation 1. In tumor microenvironments, IL4I1 functions as a negative regulator of anti-tumor immunity. AHR activation by IL4I1-derived metabolites enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity 1. IL4I1+ macrophages accumulate in tumors through interferon-γ and CD40/CD40L signaling and exhibit immunosuppressive characteristics 3. Notably, IL4I1+ macrophages phagocytose dying cells in high-turnover areas and predict favorable outcomes in colon cancer, contrasting with other macrophage populations 4. Beyond tumor immunity, IL4I1 suppresses T-cell activation and promotes regulatory T-cell differentiation through tryptophan catabolism and downstream AHR signaling 5. It regulates B-cell development and M2 macrophage polarization. IL4I1 associates with reduced survival in glioma patients and represents a promising immunotherapy target, particularly as immune checkpoint blockade induces its expression and IDO1 inhibitors do not block IL4I1 16.