Oncotarget

Research Papers:

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 and Haidong Dong

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Oncotarget. 2016; 7:70223-70231. https://doi.org/10.18632/oncotarget.11833

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Abstract

Peng Yin1, Xin Liu2, Aaron S. Mansfield3, Susan M. Harrington1, Yinghua Li2, Yiyi Yan3, Haidong Dong1,2

1Department of Urology, Mayo Clinic, Rochester, MN, USA

2Department of Immunology, Mayo Clinic, Rochester, MN, USA

3Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA

Correspondence to:

Haidong Dong, email: Dong.Haidong@mayo.edu

Keywords: CpG ODN, IL-12, immune checkpoints, PD-1, tumor immunotherapy

Received: February 29, 2016    Accepted: August 24, 2016    Published: September 02, 2016

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 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.


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