ST. LOUIS — Asthma sufferers may actually hold the key to preventing deadly brain tumors, according to a new study. Researchers from Washington University School of Medicine in St. Louis have discovered why people with the breathing condition are less likely to develop these potentially fatal growths.
Study authors found their answer in the behavior of the T cells, immune cells which fight off disease. In people with asthma, the immune system activates its T cells, but this response actually induces more inflammation in the lungs. Strangely enough, scientists say this is good news for brain research because the T cell behavior also prevents tumor growth.
Researchers believe that they may be able to reprogram T cells within brain tumor patients to act like the ones within asthma patients and stop further tumors from developing.
“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease,” says senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology, in a university release. “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? These findings open the door to new kinds of therapies targeting T cells and their interactions with cells in the brain.”
So, where’s the genetic link between asthma and tumor growth?
Study authors note that scientists first started looking at a possible link between inflammatory diseases like asthma or eczema and brain tumors 15 years ago.
Gutmann — an expert on a series of genetic disorders which cause tumors to form on nerves throughout the brain and body (neurofibromatosis) — notes that children with NF type 1 develop a certain type of brain tumor called an optic pathway glioma. These tumors form in the optic nerves which carry signals between the eyes and brain. However, Gutmann’s research from five years ago found that his patients with asthma were less likely to experience serious tumor growth.
Now, lab studies have discovered how important immune cells are in the growth of optic pathway gliomas. Study first author and postdoctoral researcher Jit Chatterjee began by studying mice genetically engineered to carry a mutation of the NF1 genes. This gene variant makes it much more likely that the animals will develop optic pathway gliomas by the time they’re three months-old.
Next, the team exposed the mice to irritants which trigger asthma at four to six weeks of age, while treating a control group with saltwater instead. Between three and six months, the researchers started examining the mice for brain tumors. Results show mice with asthma did not form any optic pathway gliomas.
Decorin is the key
The study finds that triggering asthma in tumor-prone mice changes the behavior of the animals’ T cells. Specifically, their T cells started to secrete a protein called decorin, which asthma researchers know very well.
Decorin is a major problem for asthma sufferers. The protein interacts with tissues that line the airways and makes asthma symptoms even worse. However, Chatterjee and Gutmann discovered that decorin has a beneficial effect on the brain. The protein acts on the brain’s immune cells (the microglia) and blocks them from activating and interfering with the NFkappaB activation pathway.
The team notes that when the microglia activate, they actually promote the growth and development of brain tumors. Using decorin or another substance which inhibits the NFkappaB pathway called caffeic acid phenethyl ester (CAPE) protected the genetically modified mice from growing tumors.
“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,” Gutmann, a professor of genetics, neurosurgery, and pediatrics, concludes. “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.”
The study is published in the journal Nature Communications.