Study reveals strategy to boost immune response to viral infections

The immune system, including T-cells, is known to be compromised by severe viral infections and cancer, a condition known as immune ‘exhaustion’. The development of new drugs for cancer or severe viral infections has a major focus on overcoming immune fatigue. Melbourne researchers have discovered a strategy to boost the immune response to severe viral infections, according to a study published in the journal ‘Immunity’.

A team from the Peter Doherty Institute of Infection and Immunity (Doherty Institute) led by Dr Sarah Gabriel from the University of Melbourne, Dr Daniel Utzschneider and Professor Axel Kallies has managed to identify why immune exhaustion occurs and how it can be overcome. The team previously found that some T-cells lost their function and became exhausted within days, while others, called Tpex cells, were able to maintain their function for longer periods of time.

“This idea that you need to overcome exhaustion and improve T cells is at the heart of immunotherapy,” Professor Kallies said. “Even though immunotherapy works very well, it’s only effective in about 30 percent of people. By finding ways to trigger T-cells differently so they can work effectively in the long term, we might be able to make immunotherapy more effective in more people,” he added.

In their latest work published today in Immunity, the team has now identified a mechanism that explains how Tpex cells can maintain their fitness over long periods. Professor Kallies says this discovery has the potential to improve the success rate of immunotherapy.

“We found that the activity of mTOR, a nutrient sensor that coordinates cellular energy production and consumption, was reduced in Tpex cells compared to those that were depleted,” said Dr. Gabriel. “This means that the Tpex cells were able to moderate their activity so they could remain functional for longer – it’s like going slower if you have the endurance to run a marathon instead of a full-speed sprint.”

dr. Utzschneider emphasized that flipping this switch on the immune system is a balancing act. “You don’t want to dampen the reaction too much to the point where the reaction becomes ineffective — you don’t want to stay in the race,” Dr. Utzschneider said.

“The next step was to find the mechanism that made this possible. We found that Tpex cells were exposed to increased amounts of an immunosuppressive molecule, TGF?? early in the infection. This molecule essentially acts as a brake, reducing the activity of mTOR and thereby dampening the immune response .” Excitingly, researchers have been able to use this discovery to improve the immune response to severe viral infections.

“When we treated the mice early with an mTOR inhibitor, it resulted in a better immune response later in the infection,” Dr. Gabriel said. “In addition, mice treated with an mTOR inhibitor responded better to checkpoint inhibition, a therapy widely used in cancer patients.” (ANI)

(This story was not edited by Devdiscourse staff and was automatically generated from a syndicated feed.)

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