Mechanisms of natural killer cell cytotoxicity

Published on January 31, 2023   37 min

A selection of talks on Oncology

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0:00
Hello, my name is Carsten Watzl and I'm from the Leibniz Research Centre in Dortmund in Germany, and I work with natural killer cells. The subject of this presentation will be the mechanisms of natural killer cell (NK) cytotoxicity - how NK cells kill other cells.
0:20
The best way to introduce this subject is to actually show you a video that we made in our lab. Here you see tumor cells that are labeled in green and NK cells that are labelled in red. When we start the video you see that the NK cells attach themselves to the tumor cells and kill these tumor cells by direct cellular contact. They kill the tumor cells by inducing classical apoptosis, so you see the hallmarks of apoptosis, so the cell shrinking and the membrane blebbing. Over the time course of these three hours, the NK cells have killed many of the tumor cells in this video. You can see that the NK cells cytotoxicity is a rather potent mechanism, and it's one of the major functions of these innate lymphocytes. The NK cells cytotoxicity is actually also being used therapeutically when we're talking about CAR T-cell, so other cancer immunotherapies. Therefore, it is important to understand how NK cells actually kill tumor cells.
1:22
NK cells are not just killers, they're actually serial killers, so they can kill multiple targets, but they can only kill one target at a time. This is what you see in these images that are also taken from a video that we made. Again, the NK cell here is labelled in red and the tumor cells are not labeled, but they will turn green when they die. You see in the upper left picture that the NK cell makes contact to tumor cell number one, and then this cell turns green, indicative of this cell dying and being killed by the NK cell. Then the NK cell makes contact with tumor cell number two, kills this one, and so on. So over the time course of 12 hours here, the NK cell has killed five individual target cells in a strictly serial fashion. I'll get to that in a minute why the NK cells can only kill one target at a time.

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