Expression of Receptor Tyrosine Kinases on Peripheral Blood Lymphocyte Subpopulations in Patients with Renal Cell Carcinoma and Healthy Volunteers

Abstract

Introduction: tyrosine kinases receptors (RTKs) play an important role in the pathogenesis of renal cell carcinoma (RCC). RTKs were studied on tumor and endothelial cells, but the presence of these receptors on lymphocytes was not confirmed. The objective of this study was to investigate the expression of tyrosine kinases receptors on lymphocyte subpopulations in healthy volunteers and RCC patients before and after removal of the primary tumor.Materials and methods: the study included 19 patients with pT1‑T3N0 / N+M0 / M+ RCC, subjected to nephrectomy, and 10 healthy volunteers. Blood samples were collected once from healthy donors and twice from RCC patients, immediately before and 180 days after surgery. Isolation of lymphocytes and flow cytometry were carried out using standard methods. A comparative analysis of RTKs expression levels in peripheral lymphocytes from healthy volunteers and RCC patients, as well as in RCC patients before and after the operation, was carried out. A search was performed for correlations between the initial RTKs expression on lymphocytes from RCC patients and characteristics of the tumor development, as well as the disease prognosis.Results: VEGFR-1, -2, -3, FGFR2, PDGFRα, β RTKs are expressed on CD45+ peripheral blood mononuclear cells, as well as subpopulations of CD3+ and CD8+ lymphocytes in healthy volunteers and untreated patients with RCC. No differences in the expression levels of all studied RTKs between subpopulations of lymphocytes were found in RCC patients (p > 0.05 for all). The level of RTKs expression on CD45+ peripheral cells in RCC patients before treatment is significantly lower than in healthy volunteers (p < 0.05 for all). The degree of a decrease in RTKs expression correlated with the pT status and the presence of tumor-associated venous thrombosis. A significant increase in the expression levels of VEGFR1 (on CB45+) and VEGFR2 (on CD8+, CD3+) (p < 0.05 for all) was noted 180 days after the removal of the primary tumor in patients with RCC. No other significant changes in RTKs production were identified. We were not able to determine the effect of RTKs expression on the RCC outcome.Conclusions: lymphocytes express RTKs, their expression is more pronounced in healthy people than in patients with RCC. After surgical treatment, the RTKs expression becomes restored.