TLR-activated plasmacytoid dendritic cells inhibit breast cancer cell growth in vitro and in vivo.

Jing Wu,Mingyou Zhang,Yong-Jun Liu,Yuan Qiao,Shuang Li,Yang Yang,Jingtao Chen,Shan Zhu

doi:10.18632/oncotarget.14315

Jing Wu, Mingyou Zhang + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.14315

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Journal: Oncotarget	Publication Date: Dec 28, 2016
Citations: 46	License type: cc-by

Affiliation: First Hospital of Jilin University

Abstract

Plasmacytoid dendritic cells (pDCs) are a unique subset of naturally occurring dendritic cells, which triggers the production of large amounts of type I interferons (IFNs) after viral infections through Toll-like receptor (TLR) 7 and TLR9. Recent studies have demonstrated that the activation of pDCs kills melanoma cells. However, the role of activated pDCs in breast cancer remains to be determined. In the present study, we generated mouse models of breast cancer and demonstrated that activated pDCs can directly kill breast tumor cells through TRAIL and Granzyme B. Furthermore, we established that pDCs initiate the sequential activation of NK cells and CD8+ T cells, and ultimately inhibit breast tumor growth. Understanding the role of activated pDCs in breast cancer may help to develop new strategies for manipulating the function of pDCs and induce anti-tumor immunity in breast cancer.

Highlights

Immunosurveillance can protect humans from tumor development
Dendritic cells (DCs) are generally divided into myeloid dendritic cells and plasmacytoid dendritic cells [2]. mDCs are key regulators for maintaining the balance of immunity and tolerance due to their ability to prime B and T lymphocytes, the effector cells of the immune response [3, 4]. pDCs play a key role at the interface of innate and acquired immunity in anti-viral responses by sensing viral infection through Toll-Like Receptors (TLRs) TLR7 and TLR9, which results in the production of large amounts of type-I interferons (IFNs) [5]
We used Giemsa staining to determine the morphological changes of pDCs after activation with IMQ and CpG (Figure 1A), and flow cytometry was used to detect www.impactjournals.com/oncotarget phenotypic changes associated with activation of pDCs (Figure 1B)

Summary

Introduction

Immunosurveillance can protect humans from tumor development. Tumors sometimes progress and escape through the immunosurveillance processes [1]. Dendritic cells (DCs) are antigen-presenting cells that play a critical role in linking innate and adaptive immune response. DCs are generally divided into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) [2]. MDCs are key regulators for maintaining the balance of immunity and tolerance due to their ability to prime B and T lymphocytes, the effector cells of the immune response [3, 4]. PDCs play a key role at the interface of innate and acquired immunity in anti-viral responses by sensing viral infection through Toll-Like Receptors (TLRs) TLR7 and TLR9, which results in the production of large amounts of type-I interferons (IFNs) [5]. PDCs have been shown to mediate tolerance to airway antigens, oral antigens, and cardiac allografts, which is consistent with their antigen presentation capabilities [6, 7]

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