TLR Stimulation during T-cell Activation Lowers PD-1 Expression on CD8⁺ T Cells.

ABSTRACT: Expression of T-cell checkpoint receptors can compromise antitumor immunity. Blockade of these receptors, notably PD-1 and LAG-3, which become expressed during T-cell activation with vaccination, can improve antitumor immunity. We evaluated whether T-cell checkpoint expression could be separated from T-cell activation in the context of innate immune stimulation with TLR agonists. We found that ligands for TLR1/2, TLR7, and TLR9 led to a decrease in expression of PD-1 on antigen-activated CD8⁺ T cells. These effects were mediated by IL12 released by professional antigen-presenting cells. In two separate tumor models, treatment with antitumor vaccines combined with TLR1/2 or TLR7 ligands induced antigen-specific CD8⁺ T cells with lower PD-1 expression and improved antit

SUBMITTER: Zahm CD 

PROVIDER: S-EPMC6215515 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature