Alteration of early dendritic cell activation by cancer cell lines predisposes immunosuppression, which cannot be reversed by TLR4 stimulation

Acta Biochim Biophys Sin (Shanghai). 2016 Dec;48(12):1101-1111. doi: 10.1093/abbs/gmw102. Epub 2016 Oct 19.

Abstract

Dendritic cells (DCs) have shown promise for use in cancer vaccine and cancer immunotherapy studies. However, we demonstrate that cancer cell lines can negatively interfere with DC generation in granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived cultures, although cancer cells are able to enhance CD80 cell surface activation marker and cytokine secretion. Furthermore, in the presence of cancer cells, GM-CSF-derived DCs are unable to stimulate T-cells. Additional stimulation with toll-like receptor 4 cannot fully reverse the suppressive effect of cancer cells or supernatant. Hence, it is imperative to understand the immunosuppressive effects of cancer on DCs in order for DC-based cancer immunotherapy to be successful.

Keywords: GM-CSF; cytokines; dendritic cells; early dendritic cells.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Immune Tolerance*
  • Immunotherapy
  • Lipopolysaccharides / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Toll-Like Receptor 4 / agonists*

Substances

  • Lipopolysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Granulocyte-Macrophage Colony-Stimulating Factor