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A team of scientists in Vienna, including an Irish researcher, has made a substantial breakthrough that could help us fight cancer in a new way.
The foundational work by the winners of this year’s Nobel Prize for Medicine has helped a team of scientists from the Institute of Molecular Biotechnology (IMBA) in Vienna find a way to tweak our immune system to better fight autoimmune diseases, and even cancer.
The team includes Cavan native Shane Cronin, a postdoctoral fellow at IMBA and Harvard who is first author of the paper detailing the team’s findings in Nature.
The breakthrough involves the T cells that are the fundamental building blocks of our immune system. In this case, the scientists found that in order for the T cells to do their job, they require a molecule that is long known to play an important role in the nervous system.
Within the brain, this molecule, known as tetrahydrobiopterin (BH4), is needed to produce serotonin or dopamine, often referred to as the ‘happiness hormone’. In the immune system, however, BH4 plays a very different role.
As T cells act as the ‘soldiers’ of our immune system, they try to seek out pathogen-infected cells or aberrant cells that could become tumours. When they do come into contact with such cells, T cells spread rapidly as they enter ‘combat mode’. And, just like a battle, there is often collateral damage among healthy cells, leading to autoimmune diseases such as colitis, asthma, multiple sclerosis, arthritis or certain skin diseases.
Now, the scientists have discovered that BH4 plays a critical role in controlling the growth of T cells by regulating iron and mitochondrial metabolism, explaining previous research that showed people with iron deficiency or anaemia often suffer from immune problems.
‘Truly amazing’
Josef Penninger, founding director of the study, described the discovery as “truly amazing”.
“Since it regulates not early activation but how T cells grow, the possibilities for medical applications are extremely varied; from controlling autoimmune diseases, asthma and allergies, to having a new way to trigger anti-cancer immunity!” he said.
BH4 can now be used as an important candidate for future cancer immunotherapies, as tests in mice showed that higher levels of the molecule activate the spread of T cells, causing the tumours to shrink.
To the surprise of the team, it was also shown that kynurenine – a molecule that can turn off the immune system in tumours – blocks T cell growth, but can be overcome by BH4. This allows T cells to escape local immunosuppression in the tumour environment.
So, by dialling BH4 down, it is possible to block T cell proliferation in autoimmune diseases or asthma. Yet when you dial up BH4, it can trigger T cells to grow and attack tumour cells, even under adverse conditions.
With the successful development of a potent and orally available drug, the scientists believe this new concept can be soon tested in human patients.
