Two-faced VISTA
Scientists have found out how an important element of the immune system prevents it from fighting cancer
Scientists from Dartmoor have investigated how the VISTA molecule involved in regulating the immune response prevents the immune system from attacking cancer cells. An article about this was published in the new issue of Science (ElTanbouly et al., VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance).
In their paper, the authors describe how VISTA regulates T-cell responses. VISTA (V-domain Ig suppressor of T-cell activation, V-domain immunoglobulin suppressor of T-cell activation) is one of the "control points" of the immune response. This molecule is expressed in large quantities in lymphocytes infiltrating tumors. In combination with antibodies VISTA suppresses the proliferation of tumor cells.
In addition, VISTA restricts the early stages of activation of naive T-lymphocytes, thereby preventing the development of autoimmune diseases. This molecule, for example, plays an important role in the survival of transplants, restraining the immune response against the transplanted organ.
T-lymphocytes are the basis of the body's immune system. They are divided into several types, each of which has a specific role in the immune response. For example, T-killers destroy cancer cells and cells affected by parasites. T-helpers recognize foreign antigens and activate killer cells and other lymphocytes. And T-suppressors carry out the central regulation of the immune response, controlling its strength and duration.
Like any system, the immune system needs a certain balance and a system of "checks and balances". It is provided by T-suppressors that muffle the activity of T-killers and T-helpers so necessary to combat the external threat. If the latter are not effectively managed, they begin to behave like any out-of-control power structure: suspect everyone and arrange "mass shootings" of cells of their own body. Approximately this happens in autoimmune diseases.
VISTA protein binding to a receptor on the cell membrane (figure from an article in Cell Reports).
In order to prevent this from happening, the immune system uses a number of compounds to reduce immunity, one of which is the notorious VISTA. As we know, the inhibiting immune response property of this molecule is vital to the body. However, in the case of cancer, it also turns out to be fatal: cancer cells are internal antigens of the body. Deceived by their "form of allies", VISTA does not allow T-cells to attack "their own", and cancer freely devours the body with the inactivity of the immune system.
However, there is suddenly good news in this: over the past 10 years, which the Dartmoor team has been searching for target molecules such as VISTA and the mechanisms of their work, scientists have advanced in the development of antibodies to VISTA.
"We've learned that keeping your immune system at rest is a complex and very active process," says team leader Dr. Randolph Noel. Having analyzed in detail the role of VISTA in the immune system, scientists were able to come to the conclusion that the specific blocking of this molecule will give patients a chance. "Like other negative checkpoint regulators, blocking VISTA in cancer can enhance the host's ability to create protective, tumor–specific immune responses," explains Noel.
Thus, if the planned clinical trials of a VISTA-specific antibody are successful, disabling VISTA for the duration of cancer treatment will allow the immune system to effectively attack cancer cells. This will help greatly advance cancer therapy.
Portal "Eternal youth" http://vechnayamolodost.ru