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Assembly within the tumour centre

5 Aug 2020
Assembly within the tumour centre

Both in the periphery and the centre of lung tumours, characteristic accumulations of certain white blood cells, known as macrophages, are often found.

In this case they are called tumour-associated macrophages.

There are two populations with opposite effects on the tumour: while one is tumour-promoting, the second macrophage population inhibits cancer growth.

Scientists from the Max Planck Institute for Heart and Lung Research and the Justus Liebig University in Giessen have now been able to show that identifying the position and density of the two cell populations in the tumour tissue make it possible to predict the course of the disease.

Their research is published in the journal Cancer Research.

This discovery may lead to new therapeutic possibilities.

Immune cells significantly influence the course of tumours.

Depending on the cell type, they can both promote and inhibit tumour growth.

This is particularly true for a group of macrophages, which accumulate in the tumour centre or the peripheral areas in sometimes large numbers.

Depending on their activation state, these so-called tumour-associated macrophages can have a positive or negative influence on the course of the disease.

Scientists at the Max Planck Institute for Heart and Lung Research and the Justus Liebig University in Giessen discovered that the accumulation of a subpopulation of tumour-associated macrophages in a certain area can lead to conclusions about the further course of the tumour disease.

Rajkumar Savai, project leader in the department "Development and Remodelling of the Lung" and member of the Centre for Internal Medicine at Justus Liebig University explains:

"With lung tumours, it is usually possible to distinguish the centre of the tumour from the peripheral area. Because a particularly large number of immune cells migrate to the latter, we refer to this area as the invasive tumour margin".

For their study, the researchers used an elaborated microscopy technique known as multiplex immunofluorescence microscopy.

By this technique, macrophages could be safely identified.

Furthermore their distance from neighbouring tumour cells was analysed.

In addition, the Max Planck researchers divided these cells into tumour-promoting and tumour-inhibiting tumour-associated macrophages based on certain properties.

"We found that more tumour-promoting cells were found in the invasive border area of the tumour than tumour-inhibiting cells. Moreover, they were located more adjacent to the tumour cells," said Savai.

"Based on tissue samples from more than a hundred patients, we were then able to identify a pattern."

According to this study, the survival rate in lung cancer patients was lower, in particular when the tumour-promoting macrophages in the invasive marginal areas were particularly close to the tumour cells and at the same time tumour-inhibiting macrophages were further away.

The cell number also had an influence on the prognosis of the patients:

"If there were fewer tumour-inhibiting macrophages in the tumour centre, patients had a lower probability for surviving. Overall, we found more tumour-promoting macrophages than tumour-inhibiting macrophages," Savai said.

The fact that tumour-promoting and tumour-inhibiting macrophages actually have different activity patterns was shown when the Bad Nauheim scientists sequenced the cells' RNA.

"We found that the two cell variants had very different gene expression profiles, even when compared with macrophages from outside the tumour tissue," said Savai. The researchers identified five candidates for biomarkers that could be used to predict survival in lung cancer.

"These biomarkers could prove to be very helpful for the individual treatment strategy of lung cancer patients," emphasizes Friedrich Grimminger, head of the Giessen Lung tumour Center and director of the Medical Clinic IV/V at Justus Liebig University.

"Based on characteristic gene expression profiles of the tumour-associated macrophages, we have also identified factors in this study that offer themselves as new target structures for specific therapeutic approaches," adds Werner Seeger, Director of the Department "Development and Reconstruction of the Lung" at the Max Planck Institute and the Medical Clinic II of Justus Liebig University.

Source: Max-Planck-Gesellschaft