Details

Autor(en) / Beteiligte

• Yin, Peng
• Liu, Xin
• Mansfield, Aaron S
• Harrington, Susan M
• Li, Yinghua
• Yan, Yiyi
• Dong, Haidong

Titel

CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1

Ist Teil von

• Oncotarget, 2016-10, Vol.7 (43), p.70223-70231

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2016

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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 CpG-induced 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.