THE EFFECT OF IPILIMUMAB ON THE SUBPOPULATION STRUCTURE OF LYMPHOCYTES OF PATIENTS WITH METASTATIC MELANOMA
Authors: Z.G. Kadagidze, T.N. Zabotina, O.V. Korotkova, D.V. Tabakov, A.I. Chertkova, A.A. Borunova, I.O. Panchuk, I.V. Samoilenko, G.Yu. Kharkevich, L.V. Demidov
Using of targeted drugs based on monoclonal antibodies directed against inhibitory receptors on T-cells (called «checkpoint of immunity») is a promising direction in immunotherapy of malignant tumors in our days. One of the first medicine of this group introduced in clinical practice is Ipilimumab (anti-CTLA-4).
The aim of the investigation is the study of the subpopulation structure of circulating lymphocytes of patients with metastatic melanoma in the process of Ipilimumab therapy and it’s relationship with the clinical effect of the treatment.
Materials and methods. Immunophenotyping of circulating lymphocytes was assessed by multiparameter cytometricanalysis using commercial monoclonal antibodies to surface antigens CD45, CD4, CD8, CD19, CD16, CD56, CD25, CD127, CD11b. The study included 120 patients with metastatic melanoma. Immunological tests were performed before and after 4 doses of Ipilimumab (3 mg/kg every 21 days).
Results. The study has identified the correlation of certain populations of peripheral blood lymphocytes with the life expectancy of patients treated with Ipilimumab. The main differences were observed between the group of patients with a maximum life expectancy (over 2 years) and groups of patients with life expectancy less than 2 years. Differences was shown on cells of adaptive and innate immunity, including effector cells (CD8+, CD4+T-cells, NK-cells) and regulatory cells (NKT-cells, CD8+CD28- and CD4+CD25+CD127low/neg T-suppressor cells). Under the influence of Ipilimumab therapy the most significant changes in linear subpopulation structure of circulating lymphocytes was also observed in patients withlife expectancy more than 2 years.
Conclusion. The study found the relationship of the initial amount of effector and regulatory populations of lymphocytes
in the peripheral blood with a life expectancy of patients with metastatic melanoma treated with Ipilimumab.