Neurologists in the United States think they have finally figured out why people with asthma seem to develop fewer brain tumors. The findings could one day help us develop better treatments for both conditions.
The curious connection between asthma and brain tumors first began popping up in global epidemiological research about 15 years ago, but without a proper mechanism linking the lung condition to the brain condition, some experts have dismissed the findings as random.
A new study now suggests the relationship may be real after all.
In 2015, neurologists published a study noting some children genetically prone to tumors along their optic brain pathway were not developing asthma at the same rate as you’d expect from the general population.
Further research in the lab found evidence these children’s’ tumors were being driven by an interaction between the optic nerve and some immune cells in the brain, known as T-cells and microglia.
Given that asthma is generally considered to be a T-cell mediated inflammatory disease, neurologists began to wonder if these immune cells were how the two conditions were connected.
To test the idea, researchers turned to mouse models. After genetically modifying the mice so that they were prone to optic nerve tumors, the authors induced asthma among litters at 4 and 6 weeks of age.
Curiously enough, the mice with induced asthma did not show evidence of brain tumors at 3 and 6 months. Meanwhile, those mice without asthma showed the expected development of brain cancer.
The findings suggest there’s something about asthma that hurts the lungs while helping the brain, but what is that something?
A closer look at both groups of mice has indeed revealed a distinct difference in the behavior of their T-cells.
“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease,” says neurologist David Gutmann from Washington University in St. Louis.
“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 tumor formation and growth?”
In past research, when T-cells in the lungs of mice were stopped from producing a protein known as decorin, the animals showed less inflammation in their respiratory system.
In the current study, the mice with asthma also showed an increased expression of decorin in T-cells of their spleens, lymph nodes, and optic nerves.
This matches results in humans with asthma, where the expression of decorin is similarly increased in the body’s T-cells.
In mice without asthma, however, decorin was not expressed nearly as much.
This suggests the T-cell-derived protein might not be great for the lungs, but it could have anti-carcinogenic effects in the brain.
Specifically, the authors found an increase of decorin along a mouse’s optic nerve stopped the local T-cells from activating microglia, which are sentinel immune cells known to be associated with the growth of cancerous tumors.
It’s therefore possible that treating the brain with decorin could potentially inhibit the accumulation of cancerous cells in humans, although further research will be needed to confirm these results among human children with asthma.
“We’re also investigating the role of eczema and early-childhood infections, because they both involve T-cells,” says Gutmann.
“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.”
The study was published in Nature Communications.