Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects - PubMed
5 hours ago
- #tryptophan metabolism
- #breast cancer immunotherapy
- #IDO/TDO inhibitors
- Breast cancer is often immunologically 'cold', partly due to tryptophan metabolism via the kynurenine pathway, which depletes tryptophan and accumulates kynurenine, promoting immune evasion.
- The Trp-Kyn-AhR signaling axis impairs T-cell function, induces regulatory T-cells, and affects myeloid-derived suppressor cells in breast cancer.
- First-generation IDO1 inhibitors faced clinical setbacks due to compensatory mechanisms like TDO2 upregulation, prompting development of new strategies such as dual IDO1/TDO2 inhibitors and AhR antagonists.
- Emerging approaches include nanomedicine-based delivery systems and combining tryptophan-targeted agents with immune checkpoint blockade for enhanced immunotherapy.
- The review advocates for biomarker-driven patient stratification to move towards precision metabolic immunotherapy in breast cancer.