Researchers have discovered a new population of T cells that play a critical role in maintaining the body’s immune response against chronic infections and cancer.
Their findings, published August 18th in Nature, could help to explain why immunotherapy fails in some people and the international team hope that their breakthrough could lead to the development of more effective new therapies for cancer and severe viral infections.
The researchers, led by Dr Carlson Tsui and Professor Axel Kallies from the University of Melbourne, said that the novel cell population, Tpex cells, were critical in overcoming exhaustion and maintaining long-term T cell responses during chronic viral infection.
“It has long been known that severe diseases can damage our immune system,” Dr Tsui explained.
“Known as immune exhaustion, it is a phenomenon often seen in cancer patients or patients living with chronic viral infections, such as HIV or hepatitis, that affects an immune cell population called cytotoxic T cells – which play a critical role by killing cancer cells or cells infected by a virus.
“The success or failure of immunotherapy in cancer or chronic infection depends on the quality of the T cell response, and we have been able to pinpoint the precise subset of cells that is crucial in maintaining a good response.
“These cells are like the fountain of youth for T cell immunity, allowing exhausted T cells to self-renew and remain functional.”
In previous studies Professor Kallies had identified that certain T cells resisted exhaustion and kept functioning for extended periods of time during an episode of chronic disease.
And when the Australians compared their findings with those of their partners, Dr Lorenz Kretschmer and Dr Veit Buchholz from the Technical University of Munich, who had been tracing immune responses derived from single T cells in vivo, they realised that certain memory T cell subsets had a stem-cell-like ability to self-renew.
The new study combined the unique expertise of both labs and narrowed their focus down to an extremely specific subset of Tpex cells that harboured this stem-cell-like function, which the team have dubbed ‘stem-like exhausted T cells.’
“These cells act like stem-cells for the killer T cell population; they self-renew while also producing cytotoxic T cells that can kill virus infected cells,” Dr Buchholz said.
These cells were also found to mediate the human body’s response to immunotherapy using checkpoint inhibitors, and the team were able to identify the key molecule which enables these cells to develop and function.
“We discovered a specific transcription factor, called Myb, that controls the development and function of these cells,” Professor Kallies explained.
“Without this factor, this population of cells does not form, and the T cells responding to the chronic infection cannot be maintained or respond to checkpoint inhibition. Without this transcription factor, immunotherapy fails.”
Both teams are now working on new strategies to utilise these cells and are hopeful that their research will lead to better therapies.
“Currently, immunotherapy is only successful in some cancers and only works for some patients,” Professor Kallies said.
“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.”