Health and medicine
Researchers at the Institute of Pathology at the University of Bern have now discovered a mechanism by which killer cells of the immune system can be reprogrammed. This finding could be of significance for cancer immunotherapy.
Cancer immunotherapies focus on strengthening the body's defenses. The human immune system can not only detect and fight bacteria and viruses, but also cancer cells.
The so-called natural killer (NK) cells eliminate sick cells in two ways: either by releasing cell toxins or by activating a self-destruction program. NK cells have special proteins on their surface: These dock to corresponding receptors on the target cells and thus activate their self-destruction.
Scientists call these proteins death ligands. The protein TRAIL is one of these death ligands. Tumor cells are more sensitive to TRAIL stimulation than healthy cells. Accordingly, this mechanism is considered a promising approach to trigger the self-destruction of cancer cells.
However, TRAIL appears to play a detrimental role in certain types of infections. A group headed up by Philippe Krebs from the Institute of Pathology at the University of Bern has now discovered new functions of TRAIL in viral infections. The researchers from Bern published their findings in the journal "EMBO Reports".
The Bernese researchers found that mice whose NK cells did not have TRAIL were able to fight a virus better than the control animals. The killer cells without TRAIL had reduced killer function and instead produced more messenger molecules that activate other immune cells. This means that TRAIL has a regulating and not just "destructive" function: "TRAIL therefore plays a greater role in NK cells than previously thought – if it is missing, the killer cells are reprogrammed, so to speak," says lead author Ludmila Cardoso Alves.
The findings of the researchers from Bern could be important in the fight against cancer. According to Philippe Krebs, they show an alternative way of influencing NK cells. This could be used, for example, to combine the discovered TRAIL signaling pathway with other methods against tumors.
The study was financed by the Swiss National Science Foundation, the European Union Seventh Framework Program (FP7), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement, and several private foundations.
"Our immune system consists, on the one hand, of innate immunity, the first line of defense, and, on the other, of acquired immunity, which is activated at a later stage and is responsible for immunological memory. The innate immunity can impact the acquired immunity."