Research conducted by a group of scientists in Vienna made a breakthrough that may revolutionize how we fight cancer. This research deals with T cells and tetrahydrobiopterin (BH4), a molecule previously well-known in study of biology of the nervous system and brain. This new research, however, looks into BH4’s previously unknown role in controlling growth of T cells in the immune system.
T cells play an important role in attacking pathogens such as viruses and bacteria, as well as malfunctioning cells that can cause cancer. The researchers found that genetic inactivation of GTP cyclohydrolase 1 and inhibition of sepiapterin reductase, two enzymes involved in synthesis of BH4, cause severe impairment in proliferation of T cells. The study observed this effect in mature mouse and human T cells. Ultimately, they found that altering expression of these enzymes led to increased antitumor activity in these cells.
Published in Nature, this study was led by researchers from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna and from others at the Boston Children’s Hospital in Massachusetts.
“One fascinating feature of our discovery is that a system that is actually known in neurobiology for decades can play such a key role in T cell biology,” said study co-author Josef M. Penninger, the scientific and founding director of IMBA. He states that their findings link “two completely different systems in our body” and that it “was truly amazing to find such a critical new player in T cell biology.”
He adds that it was interesting that this discovery entails control of T cell growth rather than opposing the cells activation.
The study’s authors demonstrated that reducing cell production of BH4 can severely limit T cell proliferation in mouse and human T cells. T cells appear to require BH4 to successfully regulate iron and produce energy. These findings were consistent with previous research linking iron deficiencies to complications with the immune systems.
Models of mouse cancer allowed the researchers to observe that increasing BH4 concentrations led to more T cell proliferation and tumor size decreases. BH4 appears to achieve this phenomenon occurs by overcoming kynurenine, a molecule that typically suppresses T cell growth in tumors.
These findings will likely give rise to a several medical uses, including control of “autoimmune diseases, asthma, and allergies to having a new way to trigger anticancer immunity,” Penninger stated.
Using the body’s own immune mechanisms to combat disease is becoming a growing field in medical research, with the 2018 Nobel Prize in Physiology and Medicine being granted to two scientists who developed a cancer therapy that stimulates the immune system to destroy tumor cells.
Discoveries such as these are driving a new wave of cancer treatments, potentially helping the astronomical number of cancer patients in the US. The National Cancer Institute estimates that 2018 will bring in 1,735,350 cases of cancer diagnoses and 609,640 fatalities. Novel discoveries like that of these scientists in Vienna may lead to generation of innovative treatments of cancer.
Tetrahydrobiopterin (BH4) is so cool, willing to bet theres a lot of interesting & not necessarily neurotransmitter related biology there!
The #metabolite BH4 controls #Tcell proliferation in #autoimmunity and #cancer https://t.co/6O9HEwRMnr
— DeBerardinis Lab (@RJDLab) November 9, 2018