ИСТИНА

Modern methods of treating malignant tumors often include various approaches to stimulating the antitumor activity of the immune system. So drugs based on monoclonal antibodies activate antibody-dependent cellular phagocytosis. The use of bacterial products or other stimulants of the classical activation of macrophages activates the antibody-independent cytotoxicity of the latter. At the same time, despite the success of these methods of treatment, it remains unclear why, in a large number of cases, tumor resistance to treatment develops. This can be caused both by the development of resistance of tumor cells to the antitumor activity of macrophages, and by the development of a tolerant phenotype of macrophages that do not have sufficient antitumor activity. Thus, the study of the mechanisms of interaction between tumor cells and the tumor stroma, leading both to the formation of a population of macrophages incapable of effective antitumor activity, and the selection of tumor cells resistant to the antitumor activity of macrophages, will be an extremely urgent problem of modern biomedical science. The methodological approaches that are supposed to be used in the course of work on the project include a large number of modern molecular biological and cellular techniques, including unique ones, developed by members of the scientific team. The following tasks will be solved within the framework of the proposed project. A cellular model system will be developed to analyze the formation / selection of tumor cells resistant to the antitumor activity of macrophages. The mechanisms of the formation of this resistance and their dependence on the cytotoxic activity of macrophages and on antibody-dependent cellular phagocytosis will be studied. The ability of tolerant macrophages to exhibit cytotoxic activity and antibody-dependent cellular phagocytosis will be studied. Strategies will be developed to restore the sensitivity of tumor cells to the antitumor activity of macrophages. The strategies developed will be tested in animal models to assess the potential for therapeutic use. The scientific novelty of the proposed project is due to the uniqueness of the model for studying the formation of resistance of tumor cells to the cytotoxic activity of macrophages and antibody-dependent cellular phagocytosis. All planned results can be achieved within the project. The results obtained will allow not only a better understanding of the mechanisms of interaction between the tumor and the immune system, but also allow us to propose new approaches to tumor immunotherapy.