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

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

Research output: Contribution to journalArticle

15 Scopus citations

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 languageEnglish (US)
Pages (from-to)70223-70231
Number of pages9
JournalOncotarget
Volume7
Issue number43
DOIs
StatePublished - 2016

Keywords

  • CpG ODN
  • IL-12
  • Immune checkpoints
  • PD-1
  • Tumor immunotherapy

ASJC Scopus subject areas

  • Oncology

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