A team of researchers has made a discovery that might lead to improved immunotherapy for cancer patients. By increasing the level of a molecule called 2-hydroxyglutarate, the team was able to create immune cells that were long-lived and only activated when necessary. The details are in a paper that was just published in the journal Nature.
The body’s immune system employs a number of cells to fight off pathogens. One type is the killer T-cell, which specializes in finding and destroying infected cells. Scientists are now able to create modified T-cells that are capable of detecting and fighting cancerous tumors. The problem is that killer T-cells are short-lived and often die before destroying the entire tumor. This limits the usefulness of this strategy, which is called adoptive T-cell immunotherapy.
A large international team of researchers was led by scientists from the University of Cambridge in the United Kingdom. The team worked with a molecule called 2-hydroxyglutarate (2-HG). 2-HG had previously been shown to contribute to tumor growth but the research team discovered that it had a second role. A different version of the 2-HG molecule can cause T-cells to enter a kind of sleep state. The T-cells become inactive but still “remember” identified pathogens. They can then reactivate when needed to fight off infections and tumors. T-cells enhanced with 2-HG live longer and do a better job at fighting cancer. Researchers can use this new data to create renewable killer T-cells that stick around long enough to completely destroy a tumor.
The research team found that a simple treatment of 2-HG caused killer T-cells to become long-lived and more effective at fighting tumors. The enhanced cells can switch off and then reactivate when necessary, completely renewed but with their old “memories” of pathogens. The team’s findings should lead to improved immunotherapy methods for treating cancer patients.
Tyrakis et al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature (2016).