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Some tumour cells use lactic acid to weaken the metabolism of immune cells / Therapeutic neutralization enables effective cancer control

Acute myeloid leukemia (AML) is the most common form of blood cancer in adults - and is difficult to treat. Even after a stem cell transplant, the disease returns in half of all those affected. Now, researchers at the Medical Center - University of Freiburg, in collaboration with the Max Planck Institute of Immunobiology and Epigenetics, have shown that tumor cells use lactic acid to slow down the body's immune response and how sodium bicarbonate (NaBi) converts this blockade into fuel to fight tumor cells. They published their findings on Thursday, October 28, 2020 in the journal Science Translational Medicine.

"We were able to make results from basic research very directly usable for the benefit of patients. This is very exciting to experience," says study leader Prof. Dr. Robert Zeiser, who heads the Department of Tumor Immunology at the Department of Medicine I - Hematology, Oncology and Stem Cell Transplantation at the Medical Center - University of Freiburg. In extensive laboratory experiments, the scientists demonstrated that the tumor cells in AML produce large amounts of lactic acid and release it into their environment. The acid alters the cell metabolism of the T-cells and thus prevents effective proliferation of the immune cells and an aggressive anti-tumor response.

A harmful acid becomes a nutrient for immune cells

In the mouse model, the researchers demonstrated that the effect of lactic acid can be reversed with the help of the metabolic product NaBi: "Sodium bicarbonate neutralizes the harmful effect of lactic acid and even converts it into an energy supplier for the T cells. This makes them fit to fight the tumor cells," explains first author Franziska Uhl, who conducted the study as part of her scientific doctoral thesis in Zeiser's research group at the Medical Center - University of Freiburg.

This effect was also seen in stem cell transplant patients with recurrent AML, who Zeiser and his team treated with NaBi as part of a study. NaBi is a natural base that is already approved as a drug for patients with severe AML with an acid-base balance disorder. However, its effect has not yet been investigated in conjunction with immunotherapy. "The metabolism of the T cells improved significantly as a result of the treatment," reports Zeiser. "We assume that this will make it possible to effectively combat the tumor cells. Further studies will have to show the extent to which the patients' condition improves in the long term."

Further studies on the long-term effect planned

Zeiser and his team became aware of the connection between metabolism and the proliferation and performance of certain immune cells through the work of scientists at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. "The results of our cooperation partners inspired us to take a closer look at the T cell metabolism of patients with recurrent AML," Zeiser recalls the starting point of his studies. Further studies are now to follow which, in addition to the effect of NaBi treatment on the long-term survival of patients, will also investigate the combination of the metabolic booster with other immunotherapies.

Original title of the study: Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans
DOI: 10.1126/scitranslmed.abb8969
Link to the study: stm.sciencemag.org/content/12/567/eabb8969/tab-article-info

Contact:
Prof. Dr. Robert Zeiser
Head of the Department of Tumor Immunology
Department of Medicine I (Specialty: Hematology, Oncology and Stem Cell Transplantation)
Department of Medicine I (Specialties: Hematology, Oncology and Stem Cell Transplantation)
Phone: 0761 270-34580
robert.zeiser@uniklinik-freiburg.de