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How immune cells recognize abnormal cancer cell metabolism
Sist anmeldt: 14.06.2024
When cells become tumorous, their metabolism changes dramatically. Researchers from the University of Basel and the University Hospital Basel have demonstrated that these changes leave traces that can serve as targets for cancer immunotherapy.
Cancer cells operate in turbo mode: their metabolism is programmed to multiply quickly, while their genetic material is also constantly copied and translated into proteins.
As reported by researchers led by Professor Gennaro De Libero from the University of Basel and the University Hospital Basel, this turbo metabolism leaves traces on the surface of tumor cells that can be read by specific immune cells. The research team's findings were published in the journal Science Immunology.
Immunologists working with De Libero discovered the immune cells in question, known as MR1T cells, about 10 years ago. This previously unknown type of T cells can attack and destroy tumor cells. Since then, the team has been exploring these cells as a potential tool for new immunotherapies against various types of cancer.
Modified DNA and RNA building blocks The team was able to decipher exactly how T cells recognize degenerated cells: the altered metabolism of cancer cells produces a specific type of molecule that appears on the surface of these degenerated cells.
“These molecules are chemically modified building blocks of DNA and RNA that result from changes in three important metabolic pathways,” explains De Libero.
“The fact that cancer cells have significantly altered metabolism makes them recognizable to MR1T cells,” adds Dr. Lucia Mori, who participated in the study.
In previous work, the researchers had already discovered that these T cells recognize a surface protein found on all cells known as MR1. It acts as a kind of silver platter, presenting metabolic products from inside the cell to its surface so that the immune system can check whether the cell is healthy.
"Several metabolic pathways are altered in cancer cells. This produces particularly suspicious metabolic products and thus attracts the attention of MR1T cells," explains Dr. Alessandro Vacchini, first author of the study.
The next step, the researchers intend to study in more detail how these characteristic metabolites interact with MR1T cells. Long-term vision: In future therapies, a patient's T cells could be reprogrammed and optimized to recognize and attack these cancer-specific molecules.