KYNU-related transcriptome profile and clinical outcome from 2994 breast tumors

The Catabolism of tryptophan modulates the immunosuppressive microenvironment in tumors. KYNU (Kynureninase) served as an enzyme involved in amino acid tryptophan catabolism through the kynurenine pathway. The molecular and clinical characteristics of KYNU remain unclear, and the impact of KYNU on the immune response has not been reported until now. We analyzed large-scale transcriptome data and related clinical information on 2994 breast cancer patients to characterize KYNU's role in breast cancer. There was a strong correlation between KYNU expression and major molecular and clinical characteristics, and it was more likely to be overexpressed in patients with higher malignancy subtypes. Inflammatory and immune responses were strongly correlated with KYNU. KYNU was also associated with immune modulators at the pan-cancer level, particularly its potential synergistic role with other immune checkpoints in breast cancer. KYNU expression was linked to the malignancy grade of breast cancer and predicted poorer outcomes. Tryptophan catabolism might play an important role in modulating the tumor immune microenvironment through KYNU. More significantly, KYNU might synergize with CTLA4, PDL2, IDO1, and other immune checkpoints, contributing to the development of combination cancer immunotherapy targeting KYNU and other checkpoints. As far as we are aware, this is the biggest and most thorough study describing KYNU's role in breast cancer.