Inverted neutrophils
Scientists have found a cancerous "fifth column" in the immune system of humans and mice
The so-called neutrophils, one of the components of the immune system, can play the role of a "fifth column" and help cancer spread through the human body, interfering with the work of immunotherapy and helping the tumor isolate itself from the body, according to an article published in the journal Cell Reports (Faget et al., Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer).
"Neurophiles play an important role in the fight against various pathogens, and therefore their removal from the body is unlikely to be carried out in hospitals in the treatment of cancer. We need to understand how they contribute to the development of lung cancer, which will help us create drugs that block the part of neutrophils that is responsible for the work of this "fifth column," said Etienne Meylan from the Swiss Federal Polytechnic School in Lausanne.
As scientists believe today, the immune system usually copes well with the containment of primary tumors, whose cells are inside them all the time. When cells acquire the ability to move independently, metastases occur, which for some reason the immune system simply does not see and does not try to suppress cancer cells. According to current statistics of the US medical services, about 90% of deaths of cancer patients are due to metastases.
In recent years, scientists have discovered several mechanisms that allow cancer to bypass the attention of the immune system and spread throughout the body. In some cases, its cells manage to get inside certain immune cells and force them to "transport" themselves to other parts of the body, and in other cases they "fake" a kind of molecular passport of stem cells, posing as an overgrown wound.
Meylan and his colleagues have discovered a kind of "fifth column" in the immune system that helps cancer survive at all stages of its development by observing the growth of tumor cells that are invulnerable both to the effects of chemotherapy and to experimental versions of immunotherapy that increase the "aggressiveness" of T cells and other parts of the immune system.
Having raised several mice predisposed to the development of such forms of lung cancer, scientists observed the development of the tumor and tried to understand which components of the immune system are trying to destroy cancer, and which are inactive or even interfere with the work of their comrades.
As these observations showed, tumors developed most rapidly in the body of those rodents in which the so–called neutrophils were especially active - special cells of the immune system that respond to inflammation and are responsible for the absorption and "digestion" of bacteria, as well as the production of a special set of substances that kill and repel fungi and other microbes.
As it turned out, neutrophils are a kind of "fifth column" of cancer – for reasons that are not yet clear, they accumulate at the borders of the tumor, producing substances that scare away the rest of the immune cells and force the vessels to supply less oxygen and nutrients to this part of the body. This leads to the mass death of healthy cells and the creation of comfortable conditions for the growth of cancer.
In addition, lack of food causes cancer cells to produce two protein signaling molecules that attract even more neutrophils into it, so that it begins to grow even faster. This led scientists to assume that the destruction of all or at least most of the neutrophils can slow down or even stop the growth of the tumor.
Figure from an article in Cell Reports – VM.
Guided by this idea, biologists introduced special antibodies into the body of mice, which neutralized the "fifth column", and followed their further fate. As it turned out, such therapy, despite its obvious negative effects, significantly prolonged the life of rodents and not only stopped the growth of tumors, but also reduced them by 42% in combination with immunotherapy.
Further study of these cells, scientists hope, will help to understand how they can be forced not to "betray" their native organism, and to create drugs that would help a person fight the most aggressive forms of lung cancer and other malignant tumors.
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