Targeting Metastasis by Inhibiting Breast Cancer Metabolism and Immune-Suppression
Abstract
Triple negative breast cancer (TNBC) has a particularly high rate of metastasis and the risk of recurrence after surgical removal of the primary tumor is within the first few years of initial diagnosis. A product of tryptophan breakdown called kynurenine is well-recognized as a mediator of immune suppression.. In TNBC the tryptophan catabolism pathway is induced by the enzyme tryptophan-2,3-dioxygenase (TDO2), not IDO1. TDO2 breaks down tryptophan to a product called kynurenine (Kyn), which protects tumor cells against cell death, but also when secreted from the tumor, is bad for the immune cells that should be killing tumor cells. Kyn was recently found to bind to receptors called aryl hydrocarbon receptors (AhR) in both tumor cells and immune cells and AhR promotes the ability of tumor cells survive in the bloodstream. We published that tryptophan depletion and AhR activation by Kyn decreases the survival and function of anti-tumor CD8+ T cells isolated from healthy people. We hypothesize that metabolic alterations in TNBC such as increased tryptophan catabolism are induced by anchorage independence and inflammation and result in the production of immune-suppressive metabolites, and that targeting these pathways will prevent or contain metastasis by boosting immune function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1191027
Entities
People
- Jennifer K Richer
Organizations
- University of Colorado Boulder