Cytokine-induced killer cells interact with tumor lysate-pulsed dendritic cells via CCR5 signaling

Cancer Lett. 2016 Aug 10;378(2):142-9. doi: 10.1016/j.canlet.2016.05.020. Epub 2016 May 20.

Abstract

The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level. tDCs highly expressed CCL5, which bound CCR5 expressed on CIK cells. tDCs strongly induced migration of Ccr5(+/+) CIK cells, but not that of Ccr5(-/-) CIK cells or Ccr5(+/+) CIK cells treated with the CCR5 antagonist Maraviroc. Individual tDCs contacted Ccr5(+/+) CIK cells more frequently and lengthily than with Ccr5(-/-) CIK cells. Consequently, tDCs increased the antitumor activity of Ccr5(+/+) CIK cells in vitro and in vivo, but did not increase that of Ccr5(-/-) CIK cells. Taken together, our data provide insight into the mechanism of CIK cell activation by tDCs at the single-cell level.

Keywords: Cell–cell interaction; Migration; Time-lapse imaging.

Publication types

  • Video-Audio Media
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication*
  • Cells, Cultured
  • Chemokine CCL5 / immunology
  • Chemokine CCL5 / metabolism
  • Chemotaxis, Leukocyte
  • Coculture Techniques
  • Cytokine-Induced Killer Cells / immunology
  • Cytokine-Induced Killer Cells / metabolism*
  • Cytokine-Induced Killer Cells / transplantation
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / transplantation
  • Genotype
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • RNA Interference
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Signal Transduction*
  • Time Factors
  • Time-Lapse Imaging
  • Transfection
  • Tumor Burden

Substances

  • CCR5 protein, mouse
  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Receptors, CCR5