Kynureninase in tumor immunotherapy: From mechanisms to applications

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has gradually transformed the clinical treatment landscape for most cancers as an emerging approach to tumor therapy. However, tumor immunotherapy also faces challenges posed by the immunosuppressive microenvironment. Among these, the tryptophan (Trp)-kynurenine (Kyn) metabolic axis plays a crucial role in immunosuppression by depleting Trp and accumulating immunosuppressive Kyn, thereby promoting T cell apoptosis, Treg differentiation, and impairing the efficacy of ICIs. Targeting this axis via kynureninase (KYNase) by directly degrading Kyn represents a promising strategy to reverse immune suppression. This review summarizes the structure, characteristics, and advantages of KYNase from different sources (bacteria and humans), with a focus on the recent progress in the application of KYNase in cancer therapy. Finally, we discuss the current challenges and opportunities in the application of KYNase. In the future, the deep integration of rational enzyme engineering with advanced targeted delivery technologies may resolve the core challenges in the clinical translation of KYNase, thereby truly realizing its therapeutic potential to reverse the tumor immunosuppressive microenvironment.