Diagnostic value of immunoregulatory mediators in depending on the extent of tumor growth in renal cell carcinoma
Authors:   Saratov State Medical University n.a. V.I. Razumovsky, Zakharova N.B. ,   Saratov, Russia, Ponukalin A.N. ,   Saratov State Medical University n.a. V.I. Razumovsky; Saratov, Russia, Chekhonatskaya M.L. ,   Saratov State Medical University n.a. V.I. Razumovsky; Saratov, Russia, Komyagina Yu.M. ,   Saratov State Medical University n.a. V.I. Razumovsky; Saratov, Russia, Bucharskaya A.B. ,   Saratov State Medical University n.a. V.I. Razumovsky; Saratov, Russia
Published: April 2022

Introduction. In recent years, it has been established that the study of the content of molecular genetic biomarkers in blood serum, tissues characterizing the activity of tumor-infiltrating immune cells or tumor microenvironment makes it possible to evaluate the effectiveness of immunogenic effects of antitumor therapy, as well as to predict the development of its complications. The diagnostic value of immunoregulatory mediators in peripheral blood as prognostic biomarkers of immunotherapy in patients with renal cell carcinoma (RCC) has been confirmed by a small number of studies. This limits the further development of effective strategies for the treatment of patients with renal cell carcinoma. Additional research is needed to find molecular markers. The purpose of the study – to establish the diagnostic value of changes in the serum content of tumor microenvironment mediators from the stage of the disease in patients with RCC. Material and methods. The study included 66 patients with RCC and 30 practically healthy individuals who made up the control group. Additionally, by the method of solid-phase enzyme immunoassay, the serum content of seven mediators produced by tumor microenvironment cells was determined: proinflammatory cytokines – TNFa, INFy; chemokine – MCP1; colony-stimulating factors – G- CSF GM- CSF; growth factors – VEGF, TGF-β1. Results. It was found that at the 1st and 2nd stages of the disease, the level of cytokines/chemokines and colony-stimulating factors in the blood serum increases in comparison with the group of conditionally healthy individuals, with the exception of the content of INFy. With the progression of tumor growth in patients with stages 3 and 4 of the disease, a statistically significant high content of cytokines/chemokines and colony-stimulating factors remains in the blood serum, the level of INFy decreases and the concentration of growth factors (VEGF, TGF-β1) increases. The calculated AUC data showed a good quality of the prediction model, which gives reason to consider the increase in the serum content of mediators of the tumor microenvironment of RCC as an indicator of the stage of the disease and the prevalence of tumor growth, as well as a promising laboratory marker for predicting the effectiveness of immunotherapy treatment technologies. Conclusions. The growth of tumor cells in the initial stages of RCC is accompanied by a significant increase in the content of pro-inflammatory cytokines/chemokines and colony-stimulating factors in the blood serum. During the progression of tumor growth in patients with RCC, there is an activation of the release of growth factors such as TGF-β1 and VEGF into the bloodstream. Mediators of the tumor microenvironment entering the peripheral bloodstream (cytokines/chemokines, colony-stimulating and growth factors) are prognostic indicators for evaluating the effectiveness of immunotherapy technologies for the treatment of tumor diseases.