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Foam cells in brain tumours

Foam cells visualised using confocal microscopy in tissue from a patient with glioblastoma. Shown are the nucleus (in blue), a marker for macrophages that are recruited from the bone marrow (in green) and lipid droplets that gave the foam cell its name (in white). Photo: Belting, Governa et al
Foam cells visualised using confocal microscopy in tissue from a patient with glioblastoma. Shown are the nucleus (in blue), a marker for macrophages that are recruited from the bone marrow (in green) and lipid droplets that gave the foam cell its name.

A research team at Lund University in Sweden has discovered a certain type of cells – foam cells – in patients with the aggressive brain tumour glioblastoma. It has been shown how these cells accelerate the cancer’s growth and that this can be successfully inhibited using a drug developed for arteriosclerosis.

Glioblastoma affects around 500 Swedes every year and is the most common and most aggressive form of brain tumour. On average, the survival outcome is around one year. Glioblastoma is difficult to treat for several reasons – the disease grows into the adjacent healthy brain tissue, the immune system’s cells are turned off and the efficient delivery of drugs is impeded by the blood-brain barrier.
 
“In the brain tumour field, the focus in recent years has shifted to the tumour’s microenvironment, in particular the interaction with immune cells. We have now discovered special foam cells in tumours from patients with glioblastoma. When tumour cells die and are broken down, macrophages  – a certain type of immune cells – arrive to collect fat residues and other breakdown products. When the macrophages absorb fat, they are converted into foam cells, which are a newly discovered form of immune cells in cancer,” says Valeria Governa, postdoc at Lund University and first author of the study.

Valeria Governa and Mattias Belting, photo: private
Valeria Governa and Mattias Belting. Photo: Private

The foam cells are so full of fat that they appear foamy or bubbly under a microscope, hence their name. Their original purpose is to clean tissue from cell residues, which is positive. However, in certain diseases the cells often become overloaded and instead become a factor in the development of arteriosclerosis, for example. When foam cells are in a tumour environment, this also activates mechanisms that make tumours more aggressive and worsen prospects for survival. They begin to release signal substances that facilitate the spread of the tumour by inhibiting the immune system and also promote the formation of blood vessels. 

“We are the first ones who can show in tissue from patients how these foam cells act inside the tumour. The discovery of foam cells in glioblastoma is crucial in understanding the tumour biology behind the cancer and how a diseased environment interacts with the immune system’s cells and makes them a part of the problem,” says Mattias Belting, professor of oncology at Lund University and neuro-oncology consultant at Skåne University Hospital, who led the study. 

The researchers could then take advantage of pharmaceutical substances that were previously developed for the treatment of arteriosclerosis in order to attack the foam cells’ ability to collect fat. This resulted in the inhibition of their tumour-stimulating activity. Similar mechanisms, in this case changes in the metabolism of immune cells, can drive the development of several important diseases and foam cells have also been reported in arteriosclerosis, neurodegenerative diseases and certain infectious diseases.
 
“The discovery from our research paves the way for a potentially new therapeutic approach to glioblastoma, something we will continue to study,” concludes Mattias Belting. 
 

Publication

Protumoral lipid droplet–loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted was published in Science Translational Medicine (2024)

Grants

The Swedish Research Council, Swedish Cancer Society, Swedish Childhood Cancer Fund, ALF, Mrs. Berta Kamprad Foundation, Sjöberg Foundation, and a donation from Viveca Jeppsson.
 

Contact

Mattias Belting, professor of oncology at Lund University and neuro-oncology consultant at Skåne University Hospital  
Profile in Lund University Research Portal 

Valeria Governa, postdoc at Lund University and first author of the study
Profile in Lund University Research Portal