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

Christopher D. Zahm, Viswa T Colluru, Sean J McIlwain, Irene M Ong, Douglas G. McNeel
2018 Cancer immunology research  
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 þ
more » ... 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 þ T cells with lower PD-1 expression and improved antitumor immunity. These findings highlight the role of innate immune activation during effector T-cell development and suggest that at least one mechanism by which specific TLR agonists can be strategically used as vaccine adjuvants is by modulating the expression of PD-1 during CD8 þ T-cell activation.
doi:10.1158/2326-6066.cir-18-0243 fatcat:h57baya5nbahraiqq2swgpu4ga