A stem cell transplant can be an effective treatment for patients with acute myeloid leukaemia (AML). However, the blood cancer can sometimes return. Researchers at the Medical University of Graz, working with international colleagues, have recently discovered that lactic acid – which is produced by the cancer cells and weakens the immune cells – is likely to play a key role in this.
Using nuclear magnetic resonance (NMR) spectroscopy, the scientists examined the metabolism of the cancer cells in detail. They were able to demonstrate that, in AML, the blood cancer cells produce large quantities of lactic acid and release it into their surroundings. The acid, in turn, alters the metabolism of T-cells, thereby disrupting the proliferation of these immune cells and their function.
This mechanism could play a key role in the recurrence of leukaemia following a stem cell transplant. “It was fascinating for us to see how such simple molecules can have such a major impact and deactivate the immune system,” said Tobias Madl from the University of Graz.
At the same time, the research team has found a way to neutralise this disruptive effect on T-cells: “Sodium bicarbonate neutralises the harmful effect of lactic acid and even converts it into an energy source for the T-cells. This prepares them to fight tumour cells,” reports lead author Franziska Uhl from the University Medical Centre Freiburg. By administering sodium bicarbonate – which is known for neutralising acids – T-cell function was restored in both the mouse model and in patients. Further studies are needed to determine the extent to which this improves patient survival in the long term.
References: MedUni Graz, University of Freiburg, Memorial Sloan Kettering, NY
“Metabolic reprogramming of donor T cells enhances graft-versus-leukaemia effects in mice and humans”, Science Translational Medicine, Oct. 2020. https://stm.sciencemag.org/content/12/567/eabb8969.short
