SCIENTIFIC EDUCATIONAL CENTER science idea

Scientists have determined how lymphocytes — immune cells — move between organs when they are artificially injected into the blood, for example, in the treatment of cancer. Modeling has shown that such cells, moving with blood and lymph, do not affect the circulation of natural T-lymphocytes, accumulating mainly in the spleen, liver and lymph nodes. The data obtained will help to calculate the optimal number of immune cells for patients injected with T-cell therapy. The results of the study, supported by a grant from the Presidential Program of the Russian Science Foundation (RNF), are published in the journal Frontiers in Immunology.

T cells are one of the types of lymphocytes that provide the body's immune response. They destroy tumor, mutated and foreign — for example, bacterial — cells, and also participate in the formation of "memory" of infections. Therefore, for the treatment of cancer, as well as for particularly severe infectious diseases, patients are injected with additional T cells into the vein, which help the weakened immune system fight the disease. In order for such therapy to be effective, the doctor needs to control how many T-lymphocytes enter the diseased organ or tissue with blood. To do this, you need to know how artificially injected, as well as the body's own immune cells, move. Therefore, scientists are trying to trace the routes of their migrations experimentally — on animal models — and mathematically using modeling. However, today there are "transport maps" of either only artificially injected lymphocytes into the bloodstream, or only the body's own T cells.

Scientists from the I.M. Sechenov Moscow State Medical University (Moscow) and the G.I. Marchuk Institute of Computational Mathematics of the Russian Academy of Sciences (Moscow) have created a mathematical model describing how their own and injected lymphocytes move inside the body. When developing the model, the researchers relied on the results of previously conducted experimental work, in which they tracked the movement of artificially injected and labeled with a luminous dye T-lymphocytes in the body of mice. The model also included data obtained by other scientific groups on the content of their own T-lymphocytes in various organs and tissues in healthy mice.

As a result, the researchers drew up a diagram that displayed the connections between blood, lungs, spleen, liver, as well as various lymph nodes, and derived mathematical equations describing the movement of T-lymphocytes between these organs.

The simulation showed that the introduction of additional T lymphocytes into the blood does not affect the number of own T cells in all the organs under consideration, that is, T-therapy does not disrupt the dynamics of movement of natural immune cells in the body. At the same time, the injected cells themselves are distributed unevenly: they accumulate in the spleen, liver and lymph nodes. This happens because these organs regulate the level of lymphocytes in the blood and play an important role in the formation of immunity. Thus, the total number of T-lymphocytes increases here.

In addition, the authors found that the distribution of artificially injected T cells between organs is influenced by whether these cells have a CCR7 receptor on the surface, a molecule that is responsible for the migration of immune cells to the organs of the lymphatic system. Thus, T-lymphocytes with this molecule accumulated mainly in the spleen, an organ where immune cells acquire specialization and "target" against a specific pathogen. Thus, by controlling the proportion of T cells carrying the CCR7 molecule during artificial administration, it is possible to control the number of T cells that will be ready to participate in the immune response.

The acquired knowledge can be used in cancer immunotherapy, since its main method is the introduction of additional doses of T cells into the body.

"Using the proposed mathematical model, it is possible to plan and optimize the dose of injected lymphocytes and take into account their molecular characteristics, in particular the presence of additional molecules on the surface that target cells to tumors. In the future, we plan to build a model applicable to the human body in order to assess how lymphocytes are distributed in our body during T-cell therapy," says Antonina Nikitich, a participant in the project supported by an RNF grant, a junior researcher at the Center for Mathematical Modeling in Drug Development at I.M. Sechenov Moscow State Medical University, an employee of the Institute Computational Mathematics named after G.I. Marchuk RAS.

PHOTO: One of the authors, Kirill Peskov, talks about a new project on mathematical modeling. Source: Antonina Nikitich.

Information and photos provided by the press service of the Russian Science Foundation.

The information is taken from the portal "Scientific Russia" (https://scientificrussia.ru /).