The immune system is our first and most powerful line of defense, but during long-term battles the T cell foot-soldiers can become exhausted. Now, researchers have identified a specific molecule that helps certain T cells refresh themselves, which could unlock more effective immunotherapy.
When the immune system faces an ongoing threat, such as cancer or chronic infections like hepatitis or HIV, there’s a risk that T cells can become exhausted, reducing their ability to recognize and fight off pathogens. This frustrating phenomenon is one reason that immunotherapy fails in so many patients.
The new study may lead to new ways to prevent or reverse this immune exhaustion. The researchers have previously identified a subset of T cells, named Tpex cells, which are able to keep up the fight long after other T cells have burnt out. Now the team has identified a subset of this subset, as well as the specific molecule that gives them their powers.
This group of Tpex cells were found to have an ability to renew themselves, in a fashion similar to stem cells. As such, the researchers have opted to name them “stem-cell-like exhausted T cells.”
“These cells are like the fountain of youth for T cell immunity, allowing exhausted T cells to self-renew and remain functional,” says Dr Lorenz Kretschmer, co-first author of the study.
On closer inspection, the researchers singled out a specific transcription factor called Myb, which controls the development and function of these stem-cell-like exhausted T cells.
“Without this factor, this population of cells doesn’t form, and the T cells responding to the chronic infection cannot be maintained or respond to checkpoint inhibition,” said Professor Axel Kallies, co-lead author of the study. “Basically, without this transcription factor, immunotherapy fails.”
At this stage the research remains basic, in the sense that it’s about uncovering mechanisms at play in disease and treatment. But the next steps will involve investigating whether Myb can be manipulated to reduce immune exhaustion and boost the effectiveness of immunotherapy. Other studies are exploring stem cells and genes that could play a role.
“Currently, immunotherapy is only successful in some cancers and only works for some patients,” said Kallies. “We are hopeful that our insights into the mechanisms of T cell invigoration may lead to the development of better targeted immunotherapies to improve outcomes in the context of viral infections and cancer.”
The research was published in the journal Nature.
Source: Doherty Institute