PD-1 AND TIM-3 EXPRESSION BY REGULATORY T CELLS AND INTERLEUKIN-10-PRODUCING CD4⁺ T-CELLS IN PATIENTS WITH MULTIPLE MYELOMA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
DOI: 10.22138/2500-0918-2024-21-4-422-435
P.V. Vasilchenko¹,², E.V. Batorov¹, T.A. Aristova¹, V.V. Denisova¹, D.S. Batorova¹, S.A. Sizikova¹, G.Yu. Ushakova¹, A.A. Ostanin¹, E.R. Chernykh¹
¹FSBSI «Research Institute of Fundamental and Clinical Immunology»,
Novosibirsk, Russian Federation;
²Novosibirsk State University, Novosibirsk, Russian Federation
Abstract. The paper presents an analysis of the relative content of PD-1- and TIM-3-positive regulatory T-cells (Treg) and interleukin-10(IL-10)-producing CD4⁺ T-cells in patients with multiple myeloma (MM). The aim of the study was to evaluate the content of Tregs and CD4⁺IL-10⁺ T-cells expressing the checkpoint receptors PD-1, TIM-3 and the functional activity marker CD39 in patients with MM after high-dose chemotherapy (HC) with autologous hematopoietic stem cell transplantation (auto-HSCT). Materials and methods. The study included 47 patients with MM and 27 matched donors. The content of CD4⁺CD25hiCD127ˉFOXP3⁺ Treg populations and IL-10-producing CD4⁺ T-cells expressing PD-1 and TIM-3, ectonucleotidase CD39, transcription factors eomesodermin (EOMES) and FOXP3 were assessed in peripheral blood by flow cytometry. Results. The relative content of Treg and IL-10-producing CD4⁺ T-cells was higher in MM patients compared to donors. The content of IL-10-producing T-cells was higher compared to the Treg population. The proportion of Treg expressing PD-1 and TIM-3 receptors in MM patients in remission did not differ significantly from the values in healthy donors. After НC with auto-HSCT, the content of Treg increased compared to the values before IC. The percentage of CD39⁺ Tregs was significantly higher in MM patients in remission compared to healthy donors. TIM-3⁺ Tregs were more activated compared to the PD-1⁺ population. After HC with auto-HSCT, the functional activity of Tregs significantly increased. It was found that more than 90% of IL-10-producing T-cells express the EOMES transcription factor.
Keywords: regulatory T cells, IL-10, PD-1, TIM-3, multiple myeloma
There is no conflict of interest.
Contact information for the corresponding author:
Polina V. Vasilchenko
p.vasilchenko@g.nsu.ru
Received: 01.09.2024
For citation: Vasilchenko P.V., Batorov E.V., Aristova T.A., Denisova V.V., Batorova D.S., Sizikova S.A., Ushakova G.Yu., Ostanin A.A., Chernykh E.R. PD-1 and TIM-3 expression by regulatory T-cells and interleukin-10-producing CD4⁺ T-cells in patients with multiple myeloma after autologous hematopoietic stem cell transplantation. [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2024, Vol. 21, no. 4, pp. 422–435. DOI: 10.22138/2500-0918-2024-21-4-422-435 (In Russ)
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Authors
Polina V. Vasilchenko
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
Laboratory assistant of the laboratory of cellular and molecular mechanisms of immunopathology
Novosibirsk, Russian Federation
p.vasilchenko@g.nsu.ru
Egor V. Batorov
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, senior researcher of the laboratory of cellular immunotherapy
Novosibirsk, Russian Federation
ebatorov@mail.ru
Tatyana A. Aristova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, hematologist of the Hematology Department with the bone marrow transplantation unit of the Immunopathology Clinic
Novosibirsk, Russian Federation
taris06@mail.ru
Vera V. Denisova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, head of the Hematology Department with the Bone Marrow Transplantation Unit of the Immunopathology Clinic
Novosibirsk, Russian Federation
verden@bk.ru
Darya S. Batorova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, hematologist of the Hematology Department with the bone marrow transplantation unit of the Immunopathology Clinic
Novosibirsk, Russian Federation
sugar1983@mail.ru
Svetlana A. Sizikova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, hematologist of the Hematology Department with the bone marrow transplantation unit of the Immunopathology Clinic
Novosibirsk, Russian Federation
svetlana_sizikova@mail.ru
Galina Y. Ushakova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, hematologist of the Hematology Department with the bone marrow transplantation unit of the Immunopathology Clinic
Novosibirsk, Russian Federation
bmt-novosibirsk@mail.ru
Alexander A. Ostanin
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
DM, Professor, Chief Researcher of the Laboratory of Cellular Immunotherapy
Novosibirsk, Russian Federation
ostanin62@mail.ru
Elena R. Chernykh
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
DM, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Cellular Immunotherapy
Novosibirsk, Russian Federation
ct_lab@mail.ru