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Research Article

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 and Douglas G. McNeel
Christopher D. Zahm
Carbone Cancer Center, University of Wisconsin-Madison
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Viswa T Colluru
Carbone Cancer Center, University of Wisconsin-Madison
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Sean J McIlwain
Biostatistics and Medical Informatics, University of Wisconsin-Madison
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Irene M Ong
Obstetrics and Gynecology and Biostatistics and Medical Informatics, University of Wisconsin-Madison
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Douglas G. McNeel
Medicine, University of Wisconsin Carbone Cancer Center
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  • For correspondence: dm3@medicine.wisc.edu
DOI: 10.1158/2326-6066.CIR-18-0243
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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 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.

  • Received April 11, 2018.
  • Revision received June 20, 2018.
  • Accepted August 30, 2018.
  • Copyright ©2018, American Association for Cancer Research.

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Published OnlineFirst September 10, 2018
doi: 10.1158/2326-6066.CIR-18-0243

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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 and Douglas G. McNeel
Cancer Immunol Res September 10 2018 DOI: 10.1158/2326-6066.CIR-18-0243

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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 and Douglas G. McNeel
Cancer Immunol Res September 10 2018 DOI: 10.1158/2326-6066.CIR-18-0243
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Cancer Immunology Research
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