Tumor diseases are the result of an evolutionary process in which the tumor was able to escape immune surveillance, which introduces certain difficulties in the treatment of such diseases. The emergence of a new strategy for check-point immunotherapy (ICT, check-point immunotherapy) has opened up fundamentally new ways of tumor therapy, mainly due to the ability to act on key immune system regulators that can weaken the immune response. However, most patients do not respond to treatment. To achieve an effective antitumor immune response, it is necessary to trigger a series of stepwise events, which are represented by the concept of the antitumor immune cycle. Initially, it was proposed that the immune cycle is mainly due to CD8 T cells. Further work in this area has shown the critical importance of the involvement of innate immune cells, through the activation of CD4+ T cells and NK cells. Since patients have a limited response to ICT monotherapy, it seems optimal to activate innate immune response cells in one way or another in order to expand the development of the immune cycle along the CD4/CD8 pathway. New data show a major role for intratumoral NK cells in stimulating response to immunotherapy, and efforts have been renewed to further identify and target pathways that control antitumor NK cell function. We propose to consider the possibility of strengthening ICT therapy, carried out in two ways: 1) By using specific NK cell activators: "targeted" activation of the immune cycle in an adapted bilateral tumor model. 2) By using "non-specific" activation through pattern recognition receptors. For example, a combination of an immunomodulator and an adjuvant, in an animal model with grafted tumors. To exclude factors of genetic diversity and the influence of environmental conditions, it is optimal to use animal models based on inbred mice and corresponding syngeneic linear cancer cells for such work. It is known that under certain conditions there is always a proportion of animals that do not respond to therapy, however, response / non-response outcomes have certain characteristic profiles for the tested drugs. In the case of immunotherapies, the effector molecules are proteins, so they can be genetically encoded and expressed by tumor cells - so we arrive at an idealized model in which 1) conditions are controlled; 2) the expression of immunoactivators is carried out directly at the site of exposure. Using a bilateral tumor model, it is possible to evaluate the contribution of one or another genetically encoded immune activator to ICT therapy, when co-expressed in a tumor grafted on one side. It is supposed to use the genetic modification of cancer cells for the constitutive expression of ICTs and H-cell activators. At the same time, a native cancer line is grafted onto the second side, which can act as a control for the possibility of creating conditions for triggering a generalized antitumor immune response that spreads to the entire body (abscopal effect). The study of non-specific activation is supposed to be done with the help of adjuvants, which can act as non-specific activators of pattern recognition receptors and activate innate immune cells. We will compare both models in terms of tumor growth inhibition, lifespan extension, and potential toxic effects. Pools of distinct immune cells in mice responding to therapy will be identified to construct a mechanistic model for the implementation of the immune response. Thus, for the first time we will compare two different approaches to enhancing susceptibility to ICT therapy - targeted and non-specific activation, as well as provide an evidence base to justify the choice of one or another way of activating the immune response to ICT therapy.