IMMUNOSUPPRESSIVE POTENTIAL OF PERIPHERAL REGULATORY T-LYMPHOCYTES IN THE PROCESS OF TUMOR PROGRESSION IN PATIENTS WITH METASTATIC SOFT TISSUE SARCOMAS

Abstract

In tumor microenvironment the self-maintenance condition of T-regulatory lymphocytes (Treg) are created by tumor cells due to the production of vascular endothelial growth factor VEGF and chemokine CCL2. In the present work there was evaluated the quantitative content of these proteins in cultured cell supernatants of metastatic soft tissue sarcomas (STS) as well as characterized the immunophenotype of peripheral blood Treg by flow cytometry. The study included 35 patients who received treatment at the N.N. Petrov National Medical Research Center of Oncology. For the study- samples of metastatic tumor were taken to obtain sarcoma cell culture and samples of peripheral blood of patients in the absence of tumor growth (stable disease-SD) or disease progression (PD). The statistically significant differences were found in the quantitative content of CCR10+Treg (9.1 % and 4.5 %, respectively, p=0.001), CCR4+Treg (10 % and 3.3 %, respectively, p=0.001), neuropilin-1 (Nrp1+) Treg (6 % and 4.5 %, respectively, p=0.021) in patients with PD and SD. A direct correlation of high strength was found between production of VEGF, CCL2 by metastatic STS cells and expression of Nrp1 (r=0.93, p=0.001), VEGFR-2(r=0.88, p=0.007), CCR4(r=0.81, p=0.024) by Treg cells. Statistically significant differences in the CCR10+Treg (9.5 % and 2.93 %, respectively, p=0.012) and CCR4+Treg (68, 3 % and 3.95 %, respectively, p=0.007) were detected in the group of patients with liposarcoma and synovial sarcoma. Thus in patients with metastatic STS - there was directional chemotaxis of Treg into tumor microenvironment providing the creation of tumor-induced tolerance, which could be associated with DP. The revealed regularities could be used to plan adjuvant and palliative treatment of STS patients.