Immune cells promote brain metastases


Cancer patients with metastases in the brain have very poor prognosis. A recent study from IGP shows that mast cells, a type of immune cell, are present in brain metastases and that they produce mediators that favour development of the metastases. The results show that mast cells could serve as a new target for drug development against metastases in the brain.

Despite the recent development of cancer therapies it is still difficult to treat the cancer if it has metastasised. Metastases in the brain are relatively common, especially in lung and breast cancer, and these patients have a very poor prognosis. The lack of effective therapies is party due to the unique structure of the blood brain barrier that prevents drugs from being transported from the blood to the brain tissue.

One strategy to access brain metastases could be to use the immune cells that infiltrate the brain metastases and create an inflammatory microenvironment in the tumour. This microenvironment can either stimulate or inhibit tumour development depending on which types of immune cells are present, and which types of stimulatory or inhibitory substances the immune cells produce.

In the present study the IGP researchers found that immune cells called mast cells infiltrate brain metastases where they provide a microenvironment favourable for development and progression of the metastases.

“We examined brain metastases tissues from a large group of patients with different primary tumours, for instance lung, breast, prostate or ovary cancer. We were able to detect mast cells almost in all of these tissues and the number of mast cells was higher in tissues with lung, breast and kidney cancer as primary cancer origin,” says Elena Chugunova who has led the study.

When mast cells were co-cultivated with brain metastases cells the researchers discovered that the mast cells stimulated the growth rate of the brain metastases cells. In addition, the brain metastases cells showed stem cell like properties such as an enhanced self-renewal capacity.

“The brain metastases cells thrived in the presence of mast cells, and this seems to be an effect of mediators produced by the mast cells. When the cells were co-cultivated a large number of genes were activated in the brain metastases cells. Some of these genes encode growth factors and other substances that could favour the brain metastases cell by stimulating cell growth, formation of new blood vessels and recruitment of immune suppressive cells,” says Elena Chugunova.

The fact that mast cells can infiltrate the brain metastases means that they can penetrate the blood brain barrier. This makes them ideal candidates for targeted therapy of brain metastases by using them as carriers for engineered site-specific delivery of immunostimulatory or tumour suppressive mediators to the metastases. On the other hand, the mast cell’s activation of the brain metastases must be prevented to avoid stimulation of their metastatic potential.

The present study shows that further investigations on the role of mast cells in metastatic cancer growth in the brain are warranted, and could be used to develop new treatment strategies.

The study has been published in the scientific journal Frontiers in Oncology.

More information:
Paper in Frontiers in Oncology
Elena Chugunova's research