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) |
---|---|
Pages (from-to) | 70223-70231 |
Number of pages | 9 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 43 |
DOIs | |
State | Published - 2016 |
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Keywords
- CpG ODN
- IL-12
- Immune checkpoints
- PD-1
- Tumor immunotherapy
ASJC Scopus subject areas
- Oncology
Cite this
CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1. / Yin, Peng; Liu, Xin; Mansfield, Aaron; Harrington, Susan M.; Li, Yinghua; Yan, Yiyi; Dong, Haidong M.
In: Oncotarget, Vol. 7, No. 43, 2016, p. 70223-70231.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1
AU - Yin, Peng
AU - Liu, Xin
AU - Mansfield, Aaron
AU - Harrington, Susan M.
AU - Li, Yinghua
AU - Yan, Yiyi
AU - Dong, Haidong M
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - CpG ODN
KW - IL-12
KW - Immune checkpoints
KW - PD-1
KW - Tumor immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=84994371723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994371723&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.11833
DO - 10.18632/oncotarget.11833
M3 - Article
C2 - 27602959
AN - SCOPUS:84994371723
VL - 7
SP - 70223
EP - 70231
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 43
ER -