The problem with immunotherapy is the ability of tumor cells to adapt to immune cell attacks and find ways to avoid them. One of these mechanisms is the synthesis of protein with programmed death ligand-1 (PDL1) by tumor cells. Immune cells, such as T-lymphocytes, carry 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. 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 have a significant effect. A more complete understanding of immune mechanisms is needed in order to use this knowledge to optimize and enhance the effectiveness of immunotherapy. A group of scientists from the Federal Polytechnic School of Lausanne (Switzerland) Led by Etienne Meylan, she conducted a study in mouse models to determine the “immune signature” of lung cancer. It has been found that tumor growth is promoted by neutrophils, a type of immune cells that are usually the first to react to infections, allergic reactions and bronchial asthma. In other words, they often worsen the course of the disease rather than cure it. The researchers applied the method of “neutrophil depletion” – a violation of their functions with the help of antibodies to one of the receptor proteins on their surface, and monitored 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 actually 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, as they are an important part of 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 fighting tumors and the development of more effective drugs that would block neutrophil-mediated protection of tumor cells. It has also been found that neutrophils have an effect on tumor blood vessels, resulting in hypoxia. In response, 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 Cxcl2 protein, which, in turn, increases the migration of neutrophils to the tumor. Vicious circle: snail protein promotes tumor growth and, through the Cxcl2 protein, enhances the influx of neutrophils, which cause hypoxia and the production of new snail molecules in response to it. Today, immunotherapy is the most promising direction in the treatment of oncological diseases. 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 cancer’s resistance to immunotherapy. The article by Julien Faget et al. Neutrophils and Snail orchestrate the establishment of a tumor microenvironment in lung cancer is published in the journal Cell. Aminat Adzhieva, Eternal Youth portal http://vechnayamolodost.ru according to EPFL materials: The immune cells that help tumors instead of destroying them.