MELBOURNE, Australia — The discovery of a “switch” that sends the immune system haywire may help scientists improve defenses against cancer and various viruses like COVID-19. Researchers in Australia say it makes cells overreact during severe viral infections; leading to potentially fatal blood clots and organ failure.
The team from the University of Melbourne adds the breakthrough could lead to a cure for seriously ill patients. Called, “immune exhaustion,” it also increases the risk of death in cancer patients.
Overcoming this problem is a major goal for the development of new medications. Study authors previously discovered some immune system cells, called T cells, become worn out within days. Others on the other hand, called Tpex cells, maintain function for long periods of time.
Overcoming immune exhaustion
Now, scientists have identified the mechanism that opens the door to better immunotherapy. The World Health Organization (WHO) warns vaccines alone will not beat the current or future pandemics. The world still needs drugs that treat the infection directly.
“We found that activity of mTOR, a nutrient sensor that coordinates cellular energy production and expenditure, is reduced in Tpex cells compared to those which were becoming exhausted,” says lead author Dr. Sarah Gabriel explains in a university release.
“What this means is that Tpex cells were able to dampen their activity so they could remain functional longer – it’s like going slower to have the endurance to run a marathon instead of a sprint at full speed.”
Making T cells better at fighting infections
Co-lead author Dr. Daniel Utzschneider stresses that flicking this switch to the immune system is a balancing act.
“You don’t want to dampen the response too much to the point the response becomes ineffective – you don’t want to be left walking the race,” Utzschneider says.
“The next step was finding the mechanism which was enabling this. We discovered that Tpex cells were exposed to increased amounts of an immunosuppressive molecule, TGFb, early on in an infection. This molecule essentially acts as a brake, reducing the activity of mTOR and thereby dampening the immune response.”
Moreover, the researchers harnessed the phenomenon to improve the immune response to severe viral infection.
“When we treated mice with an mTOR inhibitor early, this resulted in a better immune response later during the infection,” Dr. Gabriel explains. “In addition, mice that had been treated with the mTOR inhibitor responded better to checkpoint inhibition, a therapy widely used in cancer patients.”
The study in Immunity shows how Tpex cells maintain fitness, while T cells struggle.
“This idea that you need to overcome exhaustion and make T cells better is at the heart of immunotherapy,” co-lead author Professor Axel Kallies adds. “While immunotherapy works really well, it is only effective in around 30 percent of people. By discovering a way to prime T cells differently so they can work efficiently in the long run, we may be able to make immunotherapy more effective in more people.”
The team is now exploring this switch in preclinical cancer models.
SWNS writer Mark Waghorn contributed to this report.