Researchers understand how immune cells discover cancer’s turbocharged metabolism

When cells become tumor cells, their metabolism fundamentally changes. Researchers from the University of Basel and the University Hospital Basel have now demonstrated that this change leaves traces that could provide targets for cancer immunotherapy.

Cancer cells work in turbo mode: their metabolism is programmed for rapid proliferation, so that their genetic material is constantly copied and translated into proteins. Researchers led by Professor Gennaro Di Libero of the University of Basel and University Hospital Basel now report that this turbo metabolism leaves traces on the surface of tumor cells that can be read by specific immune cells. The research team’s findings are published in the journal Scientific Immunology.

Immunologists working with De Libero discovered the immune cells in question called MR1T cells about ten years ago. This previously unknown type of T cell can attack and eliminate tumor cells. Since then, the team has been researching these cells as a potential tool for novel immunotherapy against various types of cancer.

Modified DNA and RNA building blocks

The team was now able to understand exactly how T cells recognize damaged cells: the altered metabolism of cancer cells creates a specific type of molecule that appears on the surface of these damaged cells. „These molecules are chemically modified DNA and RNA building blocks that result from changes in three important metabolic pathways,” Di Libero explains.

„Cancer cells have a profoundly altered metabolism that makes them recognizable to MR1T cells,” says Dr. Lucia Mori, who was involved in the research. In previous work, the researchers had already discovered that these T cells recognize a surface protein found on all cells called MR1. It acts as the proverbial silver lining and delivers metabolic products from inside the cell to the cell surface so the immune system can see if the cell is healthy or not.

Several metabolic pathways are altered in cancer cells. It produces particularly suspicious metabolic products, thus alerting MR1T cells.”

Dr. Alessandro Vacchini, first author of the study

As a next step, the researchers intend to investigate in more detail how these telltale metabolites interact with MR1T cells. The long-term vision: Within the framework of future therapies, a patient’s T cells can be reprogrammed and optimized to recognize and attack these cancer-typical molecules.

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