Development of criteria for the selection of therapeutic effects on metastatic renal cell carcinoma considering the factors of tumor microenvironment.

Abstract

Introduction. Metastatic renal cell carcinoma (RCC) is the most difficult urological neoplasm form to treat. The last two decades have witnessed significant progress in the RCC treatment. A better understanding of oncogenesis has led to the development of several targeted therapies, including tyrosine kinase inhibitors (TKIs), vascular endothelial growth factor (VEGF) targeting agents, and mammalian target of rapamycin (mTOR) inhibitors. Despite the developed modern approaches to treatment and drugs with a new target action on tumor cells, the problem of treating metastatic RCC remains relevant in the world oncological science. Aim of study. Development of criteria for the selection of therapeutic effects in metastatic RCC, taking into account the factors of the tumor microenvironment. Materials and methods. The biological materials of the removed tumor tissue were studied in 110 patients with verified RCC, the first 2 groups with metastatic process, who after surgical treatment received immuno-targeted therapy in various modes, and the 3rd control group without metastases, for whom treatment was limited only to the surgical stage of treatment. Cytometry was used to identify key CD class proteins belonging to various types of immunocompetent cells.Immunohistochemical studies were performed to detect the activity of expression of tumor markers Bcl 2, Ki 67, p53 and VEGF. The histomorphological picture of extra tumor heterogeneity in RCC was studied using tumor tissue microscopy. Results. Differences in the composition of immunocompetent cells in groups with metastatic RCC and tumor tissue in patients without signs of metastatic spread indicated changes in the body's immunoreactivity at different stages, depending on the degree of tumor prevalence. The selection criteria allowing to prescribe a certain immuno/targeted therapy have been determined. Discussion. Based on the results of the analysis, we were able to establish a pathological phenotype based on the criteria of extra-tumor heterogeneity in metastatic RCC. Conclusions. Studies of the subpopulation spectrum of the tumor microenvironment have shown that differences in the quantitative and morphotypic composition of immunocompetent cells are the criterion for choosing the treatment and, together with the pathological characteristics of carcinogenesis, serve as a prognostic factor of the outcome of the disease.