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How do cytotoxic lymphocytes kill and do not get killed?

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Posted November 28, 2019

Cytotoxic lymphocytes are the real MVPs. They guard our bodies from cancerous and virus-infected cells by killing them. In this way they are aggressive defenders, but how their actions do not kill them? A new study from UCL might have found the answer.

Cytotoxic lymphocytes to you may be better known simply as white blood cells. They kill cells that may be potentially dangerous to the body. Those include cancer cells and virus-infected cells. Their aggressive defence is what protects the body from the spread of diseases. But the action how they kill those potentially harmful cells is still not very well understood.

A better understanding how cytotoxic lymphocytes work could improve outcomes of immunotherapy treatment. Image credit: Linda Bartlett via Wikimedia

Cytotoxic lymphocytes punch a hole in the side of the cell and inject it with a toxic enzyme. This incredibly useful function is protecting us from diseases. Better still, a cytotoxic lymphocyte can do it over and over again. This surprises scientists quite a bit, because those toxic enzymes cannot be good for lymphocytes themselves. Also, their hole-punching ability should also harm them as well. Looking for answers scientists studied perforin – protein responsible for the hole-punching.

Researchers found that perforin cannot damage the cytotoxic lymphocyte that it attaches to because of the envelopes of those cells. Simply put, the tighter the lipids in the outer surface of the cytotoxic lymphocyte are, the harder it is or perforin to damage the cell. When scientists attempted to disrupt that lipid layer, cells became more sensitive to perforin. Additionally, the negative charge of some lipid molecules does not allow the perforin to penetrate the cell.

Jesse Rudd-Schmidt, joint first author of the study, explained the impact of this discovery: “What we have found helps to explain how our immune system can be so effective in killing rogue cells. We are now also keen to investigate if cancer cells may use similar protection to avoid being killed by immune cells, which would then explain some of the large variability in patient response to cancer immunotherapies”.

Some tumours are very resistant to our immune cells. Immune system sometimes even struggles to find the cancerous cells. Cancer treatment in the future will rely on employing immune cells to kill tumour cells, but for that to work we need to understand why some tumours are more resistant than others to recently developed cancer immunotherapies. This research helps explain that at least partially.

It will take some time and more in-depth studies to see how cytotoxic lymphocytes work and survive their own action. Maybe eventually it will lead to new therapies that will improve their function.

 

Source: UCL

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