Journal
CANCER IMMUNOLOGY RESEARCH
Volume 6, Issue 11, Pages 1364-1374Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0243
Keywords
-
Categories
Funding
- UW Biotechnology Center
- Department of Defense Prostate Cancer Research Program [W81XWH-15-1-0492]
- NIH [R01 CA219154, T32 CA157322]
Ask authors/readers for more resources
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 thorn 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 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(+) T-cell activation. (C) 2018 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available