Abstract
CpG oligodeoxynucleotides, as a ligand of toll-like receptor (TLR)-9, have demonstrated promising antitumor effects in some clinical trials; however, its toxicity and low efficacy as a systemic therapy has limited its therapeutic applications. In order to improve its therapeutic efficacy, we investigated the mechanisms of CpGinduced antitumor immunity in the context of CD8+ T cell responses. We show that IL-12 is required for the expansion of IFN-γ producing tumor-reactive CD8+ T cells capable of rejecting tumors. In addition, CpGs reduced PD-1 expression by effector CD8+ T cells via the IL-12 pathway. The combination of CpG and PD-1 blockade show a synergistic effect in generation of systemic antitumor immunity. Our studies define a critical role of IL-12 in CpG-induced antitumor immunity and provide a rationale for combined therapy with TLR agonists and immune checkpoint blockade in cancer treatment.
Original language | English (US) |
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Pages (from-to) | 70223-70231 |
Number of pages | 9 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 43 |
DOIs | |
State | Published - 2016 |
Keywords
- CpG ODN
- IL-12
- Immune checkpoints
- PD-1
- Tumor immunotherapy
ASJC Scopus subject areas
- Oncology