Treacherous immune cells

The human immune system is supposed to protect us from cancer, but sometimes the opposite occurs. Certain immune cells become corrupted by the tumour: instead of attacking it, they actually help it grow. This treacherous collaboration is particularly evident in brain tumours and liver cancer, where it makes the development of effective treatments even more complex.

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Leila Akkari studies how cancer cells and immune cells influence each other during tumour growth. She focuses specifically on myeloid cells, a type of immune cell that is present in large numbers in brain tumours and liver cancer. These cells prove to be surprisingly changeable: sometimes they inhibit tumour growth, but often they support it instead. Remarkably, cancer cells and immune cells seem to embrace and strengthen each other – changes in one cell type directly influence the behaviour of the other. Akkari's work aims to understand how this mutual influence works and how it can be utilised therapeutically.

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Using complex genetic mouse models, Akkari made a groundbreaking discovery about a special type of macrophage (a type of immune myeloid cell) in brain tumours. These cells appear to load themselves up on fats and subsequently stimulate cancer cell growth by recycling myelin, the insulating material around nerve cells, and providing it as food to the cancer cells. This discovery connects neurobiology with cancer immunology for the first time and opens up new possibilities for treatment.

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Akkari uses advanced techniques that allow her to see exactly where and how cells in a tumour are active and which substances they produce. She combines this information from mouse models with analyses of tumour tissue from patients. Unique to her approach is that she follows the evolution of tumour cells and immune cells from the earliest stage through to therapy resistance. This integrated approach has already led to several breakthroughs in understanding therapy resistance in aggressive tumours.

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Since starting her research group in 2017, her lab has grown into a team of fifteen scientists from twelve different countries. With this diverse research group and influential collaborations, Akkari is taking important steps in the therapeutic deployment of immune cells. In the coming years, Akkari wants to investigate how she can 'reprogramme' immune cells that currently help the tumour grow so that they help fight the tumour instead. For this, she is developing new chemical tools, such as tiny fat particles similar to those used in COVID vaccines, that can specifically influence these immune cells. The ultimate goal is to be able to offer each patient personalised treatment that takes into account both the genetic characteristics of the tumour and the state of the immune system.

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