Traitor Cells

Lung cancer is one of the leading causes of death from cancer. A promising area of treatment is immunotherapy, the essence of which is to stimulate the body's immune system to fight against the tumor. Its effectiveness depends on the ability of immune cells to get inside the tumor, this has become a predictor of the prognosis for the patient.

The problem with immunotherapy is the ability of tumor cells to adapt to immune cell attacks and find ways to avoid them. One of such mechanisms is the synthesis by tumor cells of a protein with a ligand-1 of programmed death (programmed death-ligand 1, PDL1). Immune cells, for example, T-lymphocytes, carry protein-1 of programmed cell death protein 1 (PD-1) on their surface. When they try to attack the tumor, PDL1 binds the PD-1 protein, triggering a cascade of reactions in the immune cell and making it completely harmless to the tumor as a result.

Researchers are trying to overcome protective mechanisms, for example, by disabling PD-1 on the surface of immune cells in order to "confuse" tumor cells. But, unfortunately, it did not bring a significant effect. A more complete understanding of immune mechanisms is needed in order to use this knowledge to optimize and increase the effectiveness of immunotherapy.

A group of scientists from the Federal Polytechnic School of Lausanne (Switzerland) Under the leadership of Etienne Meylan, she conducted a study on mouse models, the purpose of which was to determine the "immune signature" of lung cancer. It was found that the growth of the tumor is promoted by neutrophils – a type of immune cells that, as a rule, are the first to react to infections, allergic reactions and bronchial asthma. In other words, in many cases they aggravate the course of the disease, and do not treat it.

The researchers applied the method of "depletion of neutrophils" – a violation of their functions with the help of antibodies to one of the receptor proteins on their surface, and observed the condition of the tumor. Surprisingly, the inactivity of neutrophils completely changed the behavior of tumor cells, T-lymphocytes actively destroyed them. This means that neutrophils really help the tumor hide from immune cells. This process is called "immune exclusion". Neutrophil depletion increases the sensitivity of tumor cells to anti-PD-1 immunotherapy.

In clinical practice, neutrophil depletion cannot be used, since they are an important link in human immune defense against pathogenic agents. Nevertheless, the results of the study are very useful: it is necessary to conduct a detailed study of the mechanisms of neutrophil assistance to tumor cells. This may contribute to the identification of new methods of combating tumors and the development of more effective drugs, the effect of which would be to block neutrophil-mediated protection of tumor cells.

It was also found that neutrophils have an effect on tumor blood vessels, resulting in hypoxia. In response to it, tumor cells synthesize the snail protein. It has been proven that this protein helps tumor cells survive, increases the risk of recurrence and metastasis.

In addition, the snail increases the production of the protein Cxcl2, which, in turn, increases the migration of neutrophils to the tumor.

Vicious circle: snail protein promotes tumor growth and, through the Cxcl2 protein, increases the influx of neutrophils, which cause hypoxia and the production of new snail molecules in response to it.

To date, immunotherapy is the most promising direction in the treatment of oncological diseases. But, unfortunately, up to 70% of lung cancer patients do not respond to it. It is necessary to develop methods to break the vicious circle between neutrophils and tumor cells and thus overcome the resistance of cancer to immunotherapy.

Article by Julien Faget et al. Neutrophils and Snail orchestrate the establishment of a pro-tumor microenvironment in lung cancer is published in the journal Cell.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to EPFL: The immune cells that help tumors instead of destroying them.