CXCR3-deficient natural killer cells fail to migrate to B16F10 melanoma cells.

Abstract Natural killer (NK) cells eliminate cancer cells in a contact-dependent manner. However, how NK cells find cancer cells remain unclear. Here, using time-lapse imaging, we investigated how individual NK cells migrate toward cancer cells. Although naïve B16F10 cancer cells produce low levels of chemokines, IFN-γ-treated B16F10 cells secreted high levels of CXCL10, low levels of CCL5, but did not secrete CCL2, CCL7, or CXCL12. Wild-type NK cells migrated well toward cancer cells and killed them, whereas NK cells deficient in CXCR3 did not. CXCR3-deficient NK cells also showed slower migration speed than did wild-type NK cells. Taken together, our data show that NK cells find cancer cells, at least in part, by sensing CXCL10 produced by cancer cells and suggest that a strategy to increase CXCL10 secretion by cancer cells may improve the efficacy of NK cell–based immunotherapy. Highlights • Time-lapse imaging reveals how NK cells find cancer cells. • IFN-γ activates cancer cells to produce high levels of CXCL10. • CXCL10 increases migration directionality and speed of wild-type NK cells, but not CXCR3−/− NK cells. [ABSTRACT FROM AUTHOR]