Self-renewable cancer killer cells could play critical role in immunotherapy

killer T-cells immunotherapy

In order to protect us from invading viruses and bacteria, and from internal threats such as malignant tumor cells, our immune system employs an army of specialist immune cells.

Just as a conventional army will be made up of different types of soldiers, each with a particular role, so each of these immune cells has a particular function.

Among these cells are cytotoxic T-cells (killer T-cells), whose primary function is to patrol our bodies, programmed to identify and destroy infected or cancerous cells.

Scientists are now trying to harness these cells as a way to fight cancer, by growing T-cells programmed to recognize cancer cells in the laboratory in large numbers and then reintroducing them into the body to destroy the tumor – an approach known as adoptive T-cell immunotherapy.

However, this approach has been hindered by the fact that killer T-cells are short-lived (most killer T cells are gone within three days of transfer). The army may have died out before it has managed to rid the body of the tumor.

Now, researchers from the University of Cambridge have identified a way of increasing the life-span of these killer T-cells, a discovery that could help scientists overcome one of the key hurdles preventing progress in immunotherapy.

In a paper published in the journal Nature, the researchers have identified a new role for a molecule known as 2-hydroxyglutarate, or 2-HG, which is known to trigger abnormal growth in tumor cells.

In fact, the team has shown that a slightly different form of the molecule also plays a normal, but critical, role in T-cell function: it can influence Killer T-cells to reside in a ‘memory state’.

This is a state where the cells can renew themselves, persist for a very long period of time, and re-activate to combat infection or cancer.

The researchers found that by increasing the levels of 2-HG in the T-cells, they could generate cells that effectively destroyed tumors.

Rather than expiring shortly after reintroduction, the memory state T-cells were able to persist for much longer, destroying tumor cells more effectively.

This means that rather than creating killer T-cells that are active from the start, but burn out very quickly, the researchers are creating an army of ‘renewable cells’ that can stay quiet for a long time, but will go into action when necessary and fight tumor cells.

Therefore, with a fairly trivial treatment of T-cells, researchers are able to change a moderate response to tumor growth to a much stronger response, potentially giving people a more permanent immunity to the tumors they are carrying.

This could make immunotherapy for cancer much more effective.

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Citation: Tyrakis PA, et al. (2016). The immunometabolite S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature, published online. DOI: 10.1038/nature20165.
Figure legend: This image is credited to NIAID.