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

• tDCs increase the antitumor activity of CIK cells via cell–cell contacts.
• Ccr5−/− CIK cells do not migrate to tDCs.
• Ccr5−/− CIK cells show less frequent and shorter contacts with tDCs than wild-type CIK cells.
• Time-lapse imaging reveals how tDCs increase the antitumor activity of CIK cells at the single-cell level.

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.