New technology sheds light on immune cell differences in glioblastoma

A new study by the Walmsley lab has, for the first time, identified the set of proteins that neutrophils express within a tumour to a very high level of detail. This technology has opened the door to understanding neutrophil roles in brain tumours such as glioblastoma but also more generally in health and disease states.

Neutrophils - a type of immune cell - can infiltrate and behave in very different ways inside a tumour. Some inhibit tumour growth, while others can promote growth. Genetic tools have shown that neutrophils come in many subtypes, but it is still unclear what each subtype does. 

To better understand their behaviour, the Walmsley group together with collaborators, developed and used a cutting-edge single cell proteomics platform, an advanced technology that can measure the proteins inside individual neutrophils taken from patients with glioblastoma, an aggressive brain tumour. 

The researchers analysed neutrophils from blood and tumours of six patients and were able to detect over 1,100 proteins in single neutrophils taken from tumours. Using this new technology, the researchers identified seven different subgroups of neutrophils, each representing different functional states. 

In one of these states, neutrophils appeared to be releasing proteins linked to promoting tumour growth and stopping the work of other immune cells.  Separately, a subset of neutrophils that generate sticky nets and have the potential to block the tumour blood vessels was observed. This suggests that multiple neutrophil populations can act in ways that are harmful to the host and helpful to the cancer.

This is the first time that neutrophil protein expression has been studied at a single cell level, revealing multiple neutrophil states that were invisible to previous technologies.

Overall, this study shows that neutrophils inside glioblastoma tumours are far more diverse and changeable than previously appreciated, and that studying their proteins, not just their genes, reveals important aspects of their behaviour. Being able to identify and characterise different neutrophil populations can also offer potential therapeutic targets.

The Walmsley team will now explore the location and role of these different neutrophil subsets, combining exciting new techniques such as 3D imaging. They will also further develop the single cell proteomics platform and capabilities to study neutrophils in health and chronic inflammatory disease with emphasis on chronic obstructive pulmonary disease (COPD).

This work was funded by Cancer Research UK, Wellcome Trust, Austrian Research Promotion Agency, Vienna Science and Technology and Austrian Science Fund.

Related links

Walmsley research group

Full article in Nature Communications 

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Group photo of Walmsley lab members sitting on steps within IRR
Group photo of the Walmsley lab taken at IRR

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