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

Oncotarget. 2017 Feb 14;8(7):11708-11718. doi: 10.18632/oncotarget.14315.

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.

Keywords: CpG; Imiquimod; Toll-like receptor; breast cancer; plasmacytoid dendritic cells.

MeSH terms

  • Aminoquinolines / pharmacology
  • Animals
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Dendritic Cells / transplantation*
  • Disease Models, Animal
  • Female
  • Granzymes / immunology
  • Imiquimod
  • Immunotherapy, Adoptive / methods*
  • Interferon Inducers / pharmacology
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • TNF-Related Apoptosis-Inducing Ligand / immunology
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 9 / immunology

Substances

  • Aminoquinolines
  • Interferon Inducers
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tlr7 protein, mouse
  • Tlr9 protein, mouse
  • Tnfsf10 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Granzymes
  • Gzmb protein, mouse
  • Imiquimod