A Role for Tryptophan-2,3-dioxygenase in CD8 T-cell Suppression and Evidence of Tryptophan Catabolism in Breast Cancer Patient Plasma.

ABSTRACT: Tryptophan catabolism is an attractive target for reducing tumor progression and improving antitumor immunity in multiple cancers. Tumor infiltration by CD8 T cells correlates with improved prognosis in triple-negative breast cancer (TNBC) and a significant effort is underway to improve CD8 T-cell antitumor activity. In this study, primary human immune cells were isolated from the peripheral blood of patients and used to demonstrate that the tryptophan catabolite kynurenine induces CD8 T-cell death. Furthermore, it is demonstrated that anchorage-independent TNBC utilizes the tryptophan-catabolizing enzyme tryptophan 2,3-dioxygenase (TDO) to inhibit CD8 T-cell viability. Publicly available data revealed that high TDO2, the gene encoding TDO, correlates with poor breast cancer clinica

SUBMITTER: Greene LI 

PROVIDER: S-EPMC6318037 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature