Researchers may have just stumbled upon a new way to take on brain tumours after finally figuring out why people with asthma are less likely to develop this form of cancer.
The study, published in the journal Nature Communications, explored the mysterious relationship between inflammatory diseases and brain tumours — two very different conditions — and discovered the behaviour of the body’s T cells may hold the answer. The team of researchers, from Washington University School of Medicine in St. Louis, found that when mice develop asthma, their T cells activate in a way that induces inflammation in the lungs but prevents the growth of tumours in the brain.
“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease,” said David Gutmann, the senior author of the study. “But what if we could trick the T cells into thinking they’re asthma T cells when they enter the brain, so they no longer support brain tumour formation and growth? These findings open the door to new kinds of therapies targeting T cells and their interactions with cells in the brain.”
The suspicion that inflammatory diseases are related to a reduced risk of brain tumours was first proposed around 15 years ago and largely based on epidemiologic observation. However, with no obvious link between the two conditions, many researchers doubted an association actually existed.
Gutmann began to notice an inverse relationship between the two conditions around five years ago through his study of neurofibromatosis (NF) — a set of complex genetic disorders that leads to the growth of tumours on nerves in the brain and throughout the body. He wasn’t sure what to make of the connection until more recent research in his lab identified the key role immune cells play in the formation of tumours on the optic pathways of children with NF type 1.
He began to collaborate with Jit Chatterjee, a postdoctoral researcher determined to diagnose the underlying mechanism at work. Chatterjee studied a group of mice that were engineered to carry a mutation in their NF1 genes that would result in tumours on their optic nerves by the age of three months. He exposed these mice to irritants known to cause asthma between the ages of four and six weeks and gave a saltwater solution to a control group. He found that the mice who developed asthma did not experience tumours on their optic nerves.
Further study revealed that the T cells of these mice began to behave differently after developing asthma, secreting a protein called decorin that is known to act on and irritate the lining of the airways. In the brain, however, this protein produces a very different result, blocking the activation of immune cells called microglia that promote tumour growth.
Administering decorin or caffeic acid phenethyl ester (CAPE) — a compound that also inhibits this activation pathway — was found to prevent mice from developing tumours on their optic nerves.
“The most exciting part of this is that it shows that there is a normal communication between T cells in the body and the cells in the brain that support optic pathway glioma formation and growth,” said Gutmann. “The next step for us is to see whether this is also true for other kinds of brain tumors. We’re also investigating the role of eczema and early-childhood infections, because they both involve T cells.
“As we understand this communication between T cells and the cells that promote brain tumors better, we’ll start finding more opportunities to develop clever therapeutics to intervene in the process.”
Dave Yasvinski is a writer with Healthing.ca
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