Video Catches T-Lymphocytes Killing Cancer Cells

Using spinning-disk confocal microscopy and lattice light sheet microscopy, researchers led by Gillian Griffiths, University of Cambridge, U.K., have produced a video of cytotoxic T lymphocytes (CTLs) hunting down and destroying cancerous tumor cells. Their high-resolution time-lapse multi-color imaging technique records 2-D slices of the scene and stitches them together in chronological order (Immunity, doi: 10.1016/j.immuni.2015.04.013). This video timeline could help scientists better understand the body’s immune response to cancer.  

A cytotoxic T lymphocyte (CTL) is a type of white blood cell that can identify a cancer cell and kill it by injecting it with a toxic substance. Confocal, super-resolution and electron microscopy techniques have given researchers snapshots of fixed CTLs and live CTLs, but these techniques haven’t provided a clear view of the sequence of events leading up to cancer cell death during a CTL attack. 
With spinning-disk confocal imaging, the researchers captured serial confocal 0.8-µm Z-stacks at time intervals at each Z plane. They used imaging software to stitch the stacks into 4-D data. With lattice light sheet microscopy, the team imaged the volume from 131 2-D planes of CTL-target conjugates every 1.3 seconds for hundreds of time points, which gave them high-resolution images of 3-D volumes over time (i.e., 4-D).

By combining results from both imaging techniques, the team was able to elucidate the following order of events: A CTL approaches a cancer cell and extends “feelers” to confirm that it is indeed cancerous. The CTL binds to the cancer cell and sends its cytotoxin toward the immunological synapse. Once the cytotoxin crosses the synapse, the cancer cell began to die. The CTL then detaches from the dying cancer cell and searches for another victim.

A video of CTLs killing cancer cells is available at www.youtube.com/watch?v=ntk8XsxVDi0