Killers in check
The so-called natural killer cells (NK) are cells of the innate immune system that find and kill infected or cancerous cells. A group of researchers led by Philip Krebs from the Institute of Pathology at the University of Bern has discovered a mechanism by which certain immune cells destroy target cells, which can be used to control the killer cells themselves. This discovery can improve cancer immunotherapy.
During a viral infection, NK cells also restrain the body's own immune cells, such as T lymphocytes, in order to avoid destroying intact cells of the body. In addition, NK cells release messenger molecules that support the functioning of the immune system. It is obvious that NK cells are extremely important for immunity - the presence of defective NK can lead to the development of recurrent infections and malignant neoplasms.
NK cells eliminate target cells in two ways: they either kill them by releasing cytotoxins, or activate a self-destruct mechanism in them. NK cells have special proteins on their surface, the so-called death ligands, which attach to the corresponding receptors on target cells and thereby trigger the process of self-destruction in them. The TRAIL protein is one of these death ligands that NK cells use to kill target cells. Compared to healthy tumor cells, they are more sensitive to the action of TRAIL, so it is believed that its binding to a specific receptor triggers the death of tumor cells without affecting healthy ones.
This pathway is considered a promising approach to trigger the self-destruction of cancer cells. However, TRAIL seems to play a negative role in some types of infections, and a more detailed understanding of its functions is needed. A group of researchers described the new functions of TRAIL in viral infections, which may also play an important role in the fight against cancer.
Killer cells without TRAIL become "tame"
Lyudmila Cardozo-Alves at the Institute of Pathology studied the role of TRAIL in the response to arenovirus causing lymphocytic choriomeningitis, which is a natural pathogen in rodents and often serves as a model of viral infection in immunology. Cardozo-Alves investigated the infection in mice whose NK cells did not have a TRAIL, and found that these mice were able to fight the virus better than control animals. Mice without TRAIL had more protective CD8+T lymphocytes and, consequently, they were more able to remove virus-infected cells.
The absence of TRAIL made NK cells "tame": they reduced the activity of the killers so that they produced more messenger molecules that activate other immune cells. This is due to the fact that NK cells without TRAIL perceive different signals from the environment differently. On the one hand, they are less susceptible to the trigger that causes them to release cytotoxins. At the same time, they respond more strongly to another signal, which causes them to release more messenger molecules. Thus, TRAIL plays a more important role in the activity of NK cells than previously thought. If it is absent, killer cells are reprogrammed on their own. This feature is not only characteristic of mice, the absence of TRAIL also affects human NK cells.
Possible significance for cancer immunotherapy
The results of this work can be useful in improving cancer control methods, since the detected signaling pathway regulates the function of NK cells, which, in turn, are important for the control of tumor cells. There are several modern methods of cancer treatment, the essence of which is targeting the immune system against tumor cells, studies of NK-cell reactivation in patients with tumors are being conducted. The results of the current study show an alternative way of influencing NK cells, which can be used, for example, to combine the detected TRAIL signaling pathway with other methods of combating tumors.
Article by L.Cardoso Alves et al. Non‐apoptotic TRAIL function modulates NK cell activity during viral infection published in the journal EMBO Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Bern: A new pathway to "reprogram" killer cells.