Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism.

ABSTRACT: Dendritic cells (DC) have a critical effect on the outcome of adaptive immune responses against growing tumors. Whereas it is generally assumed that the presence of phenotypically mature DCs should promote protective antitumor immunity, evidence to the contrary does exist. We describe here a novel mechanism by which tumor-infiltrating dendritic cells (TIDC) actively contribute to the suppression of protective CD8(+) T-cell-based antitumor immunity. Using the BALB/NeuT model of spontaneously arising mammary carcinoma, we found that canonical MHC II(+)/CD11b(+)/CD11c(high) TIDCs act as regulatory DCs to suppress CD8(+) T-cell function, resulting in diminished T-cell-based antitumor immunity in vivo. Stimulation of naive T cells with regulatory TIDCs resulted in an altered cell fate program c

SUBMITTER: Norian LA 

PROVIDER: S-EPMC2848068 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature