Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice

Boosting cancer therapies with natural killer cells

26 December 2018

Natural killer cells do not require glutamine as a fuel source, but they do need it for one of their key molecular switches, researchers in Ireland have discovered. This finding has implications for anticancer therapies currently being developed.

Scientists are researching therapies that target cancer cells’ ability to metabolize the amino acid glutamine — an important fuel source for many kinds of tumours. The research is promising, but it has not been clear what implications it might have for a type of cancer-killing immune cell called natural killer cells. Activated immune cells need to fuel the higher rates of metabolism required for conducting their defence-related activities, and some types of these cells need glutamine for their metabolism.

David Finlay of Trinity College Dublin in Ireland has been studying the metabolism of immune cells. He and a team of researchers investigated normal and genetically modified natural killer cells to uncover details of how their metabolic processes work. They were surprised to find that, unlike some other immune cells, natural killer cells do not need glutamine to fuel their metabolism. However, the researchers discovered that a transcription factor called cMyc, which controls the metabolic machinery in natural killer cells, does need glutamine.

“So glutamine is not a fuel for natural killer cells, but it is an important signal to keep metabolic processes turned on in them,” Finlay explains.

The team also identified a molecule called SLC7A5 as a predominant transporter of amino acids in activated natural killer cells. This transporter, along with glutamine, is needed to activate cMyc.

“Our research shows that drugs that target glutamine metabolism in tumour cells won’t disrupt the cancer-killing abilities of natural killer cells,” explains Finlay. “Also, because these drugs stop tumour cells using glutamine, there will be more in the local environment for other cells, including natural killer cells. This would be good for natural killer cells because glutamine is an important signal that is required to keep metabolic processes, and therefore cancer-killing activities, turned on in them.”

Finlay and his team suggest that a potent anticancer therapy for some solid tumours could involve injecting activated natural killer cells in addition to administering a drug that targets the glutamine metabolism of cancer cell. Further investigations in mice are needed to determine the effectiveness of this sort of treatment.

The researchers are now investigating other ways in which tumour cells might disrupt natural killer cell metabolism. They are also looking into ways to enhance natural killer cell abilities to destroy cancer cells.

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References

1. Nature Communications 9, 2341 (2018). doi: 10.1038/s41467-018-04719-2