Researchers believe they have uncovered why individuals with asthma have a lowered risk of brain tumours and how these findings could lead to new therapeutic approaches.
Asthma is a common lung condition that causes occasional breathing difficulties. It causes the airways to become narrowed and inflamed. However, people with this breathing disease seem less likely to develop brain tumours than others.
Researchers at the Washington University of Medicine in St. Louis published their findings online in Nature Communications.
T Cells prevent brain tumours
The researchers believe that T cells, a type of immune cell, become activated when an individual or a mouse develops asthma. In a new mouse study, researchers discovered that asthma causes the T cells to induce lung inflammation but prevents the growth of brain tumours.
“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease,” said senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology. “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 idea that people with inflammatory diseases, such as asthma or eczema; are less prone to developing brain tumours was first proposed over 15 years ago, based on epidemiologic observations. However, there was no reason why the two very different diseases would be linked, and some scientists have questioned whether the association existed.
Gutmann is an expert on neurofibromatosis (NF), a set of complex genetic disorders that cause tumours to grow on nerves in the brain and throughout the body. Children with NF type 1 (NF1) can develop a brain tumour known as an optic pathway glioma. These tumours grow within the optic nerves, which carries messages between the eyes and the brain. Gutmann, director of the Washington University NF Center, noted an inverse association between asthma and brain tumours among his patients more than five years ago but didn’t know what to make of it. It wasn’t until more recent studies from his lab began to reveal the crucial role that immune cells play in developing optic pathway gliomas that he began to wonder whether immune cells could account for the association between asthma and brain tumours.
Jit Chatterjee, PhD, a postdoctoral researcher and the paper’s first author, took on the challenge of investigating the association. Working with co-author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine and director of the Division of Pulmonary & Critical Care Medicine, Chatterjee, studied genetically modified mice that carry a mutation in their NF1 genes, forming optic pathway gliomas by three months of age.
Chatterjee exposed groups of mice to irritants that induced asthma at four weeks to six weeks old and treated a control group with saltwater for comparison. Then, he checked for optic pathway gliomas at three months and six months of age. The mice with asthma did not form these brain tumours.
Further experiments on tumour-prone mice
The researchers experimented further and revealed that inducing asthma in tumour-prone mice changes the behaviour of their T cells. After the mice developed asthma, their T cells began secreting decorin, a known protein to asthma researchers.
In the airways, decorin acts on the tissues that line the airways, which aggravates asthma symptoms. But in the brain, Chatterjee and Gutmann discovered, decorin is beneficial. The protein acts on immune cells known as microglia and blocks their activation by interfering with the NFkappaB activation pathway. Activated microglia promote the growth and development of brain tumours.
Treatment with either decorin or caffeic acid phenethyl ester (CAPE), a compound that inhibits the NFkappaB activation pathway protected mice with NF1 mutations from developing optic pathway gliomas. The findings suggest that blocking microglial activation may be a potential therapeutic approach for brain tumours.
“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, who is also a professor of genetics, of neurosurgery and paediatrics. “The next step for us is to see whether this is also true for other kinds of brain tumours. 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 tumours better, we’ll start finding more opportunities to develop clever therapeutics to intervene in the process.”
