TDO2 (tryptophan 2,3-dioxygenase) is a heme-dependent enzyme that catalyzes the oxidative cleavage of L-tryptophan to N-formyl-L-kynurenine, representing the rate-limiting step in the kynurenine metabolic pathway 1. The enzyme functions as a homotetramer in the cytosol and plays a critical role in tryptophan catabolism. Mechanistically, TDO2 converts tryptophan to kynurenine, which serves as a ligand for the aryl hydrocarbon receptor (AhR), activating downstream signaling pathways that promote immune suppression and tumor progression 12. This TDO2-kynurenine-AhR axis generates immune-tolerant dendritic cells and regulatory T cells, fostering a tumor microenvironment defective in cancer cell recognition 1. TDO2 is significantly upregulated in multiple cancer types, including colorectal cancer through TCF4/β-catenin-mediated transcription in APC-deficient tumors 2, and contributes to cancer cell proliferation, metastasis, and chemotherapy resistance 34. Clinically, TDO2 expression correlates with poor prognosis across various cancers 34, and TDO2 inhibitors show therapeutic promise in cancer treatment by restoring anti-tumor immunity and enhancing chemotherapy efficacy 53. The enzyme also plays a role in non-malignant conditions, as mutations affecting tryptophan metabolism are associated with hypertryptophanemia.