Abstract

Abstract Natural killer (NK) cell -mediated killing of cancer cells is essentially dependent on the direct cell-cell interaction. Using time-lapse imaging, we examine how NK cells contact melanoma cells at the single cell level. First, we analyzed contact dynamics of NK cells. Among 1,134 NK cells appeared in 36 movies in time-lapse imaging for 6 h, 121 NK cells (named competent NK, cNK) showed lytic contact with melanoma cells and 158 NK cells (named incompetent NK, iNK) showed non-lytic contact. Although contact numbers of both cell types was similar each other, the duration of contact appeared to be different. cNK cells contacted melanoma cells for 25 min without movement, but iNK cells contacted target cells for 13~14 min with moving around cancer cells. Both cell types moved at average speed of 5~6 um/min before contact and 1.6~2.1 um/min during contact. Next, we analyzed lytic process of melanoma cells, which could be described by two phases: rounding and membrane damage. Immediately after contacting cNK cells, all melanoma cells rounded up and it took 35 min (6-120) having small deviation. Then, melanoma cells lost membrane integrity and it took 103 (6-298) showing big deviation. Together, our data demonstrate that a small fraction of NK cells are cytotoxic to melanoma cells.

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