TLR7/8 agonists trigger immunostimulatory properties of human 6-sulfo LacNAc dendritic cells

Cancer Lett. 2013 Jul 10;335(1):119-27. doi: 10.1016/j.canlet.2013.02.003. Epub 2013 Feb 9.

Abstract

Imiquimod and resiquimod represent Toll-like receptor (TLR) 7 and 8 agonists, which emerged as attractive candidates for tumor therapy. To elucidate immune cells, which mainly contribute to TLR7/8-mediated antitumoral activity, we investigated the impact of imiquimod and resiquimod on native human 6-sulfo LacNAc (slan) dendritic cells (DCs). We found that both TLR7/8 agonists significantly improve the release of various proinflammatory cytokines by slanDCs and promote their tumor-directed cytotoxic activity. Furthermore, resiquimod efficiently augmented the ability of slanDCs to stimulate T cells and natural killer cells. These results indicate that imiquimod and resiquimod trigger various immunostimulatory properties of slanDCs, which may contribute to their antitumor effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology*
  • Antigens, CD / metabolism
  • Antineoplastic Agents / pharmacology*
  • B7-2 Antigen / metabolism
  • CD83 Antigen
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Screening Assays, Antitumor
  • HLA-DR Antigens / metabolism
  • HT29 Cells
  • Humans
  • Imidazoles / pharmacology*
  • Imiquimod
  • Immunoglobulins / metabolism
  • Immunomodulation / drug effects
  • Inflammation Mediators / metabolism
  • K562 Cells
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / agonists*
  • Toll-Like Receptor 8 / metabolism

Substances

  • Aminoquinolines
  • Antigens, CD
  • Antineoplastic Agents
  • B7-2 Antigen
  • CD86 protein, human
  • Cytokines
  • HLA-DR Antigens
  • Imidazoles
  • Immunoglobulins
  • Inflammation Mediators
  • Membrane Glycoproteins
  • TLR7 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Imiquimod
  • resiquimod