EXPRESSION OF NKG2 RECEPTORS ON CYTOTOXIC LYMPHOCYTES IN PATIENTS WITH MULTIPLE MYELOMA



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Abstract

This study assessed the expression of NKG2 family receptors (NKG2A, NKG2C, NKG2D) on cytotoxic T lymphocytes and NK cells from peripheral blood of patients with multiple myeloma (MM) compared to healthy donors. The relevance of this work is due to the important role of the HLA‑E/NKG2 axis in the mechanisms of tumor immune evasion in MM, as well as the potential for therapeutic blockade of these receptors. The study included 10 patients with MM (stage II–III according to Durie–Salmon, in remission) and 9 conditionally healthy donors. Flow cytometry was used to determine the relative abundance of NK cell subpopulations (CD16−CD56+, CD16+CD56+, CD16+CD56−) and CD3+CD4− cytotoxic T lymphocytes expressing NKG2A, NKG2C, and NKG2D. It was found that, compared to donors, MM patients had a significantly higher proportion of NKG2A+ cells among mature CD16+CD56+ NK cells (median 23.8% vs. 7.5%) and among CD16+CD56− NK cells (10.7% vs. 2.1%). At the same time, the proportion of CD3+CD4− cytotoxic T lymphocytes expressing the activating receptor NKG2C was reduced in MM (1.9% vs. 4.6% in donors). The relative abundance of cells expressing NKG2D did not differ between groups for either NK cells or T lymphocytes. These data indicate a shift in balance toward predominance of the inhibitory receptor NKG2A in the NK cell compartment and a reduction of the activating receptor NKG2C in the T‑cell compartment in multiple myeloma. This may reflect suppression of adaptive cellular immunity and contribute to tumor immune evasion. Thus, the HLA‑E/NKG2 axis represents a promising target for further study of the immunopathogenesis of hematologic malignancies and for the development of immunotherapeutic approaches aimed at restoring the function of effector lymphocytes.

About the authors

Ivan P. Skachkov

Federal State Budgetary Scientific Institution, “Research Institute of Fundamental and Clinical Immunology” (RIFCI), Novosibirsk, Russia

Email: pavania02@gmail.com
ORCID iD: 0009-0000-0530-3818

assistant researcher of the Laboratory of Clinical Immunopathology RIFCI

Russian Federation, 630099 Russia, Novosibirsk, Yadrintsevskaya st.,14

Alina A. Aktanova

Federal State Budgetary Scientific Institution, “Research Institute of Fundamental and Clinical Immunology” (RIFCI), Novosibirsk, Russia;
Novosibirsk State Medical University, Novosibirsk, Russia

Email: aktanova_al@mail.ru
ORCID iD: 0000-0002-2075-8551

Junior Researcher, Laboratory of Clinical Immunopathology, Assistant Professor, Department of Immunology, Faculty of Medicine

Russian Federation, 630099 Russia, Novosibirsk, Yadrintsevskaya st.,14 630091, Russia, Novosibirsk, Krasny Prospekt, 52

Vera V. Denisova

Clinic of Immunopathology (CI) of RIFCI, Novosibirsk, Russia

Email: verden@bk.ru
ORCID iD: 0000-0003-1951-2260

PhD (Medicine), Head, Hematology Department with the Bone Marrow Transplantation, Clinic of Immunopathology

Russian Federation, 630047, Russia, Novosibirsk, Zalesskogo, 6

Galina Y. Ushakova

Clinic of Immunopathology (CI) of RIFCI, Novosibirsk, Russia

Email: bmt-novosibirsk@mail.ru

PhD, hematologist at the Hematology Department with Bone Marrow Transplantation Unit at the Clinic of Immunopathology of RIFCI

Russian Federation, 630047, Russia, Novosibirsk, Zalesskogo, 6

Svetlana А. Sizikova

Clinic of Immunopathology (CI) of RIFCI, Novosibirsk, Russia

Email: svetlana_sizikova@mail.ru

PhD, hematologist at the Hematology Department with Bone Marrow Transplantation Unit at the Clinic of Immunopathology of RIFCI

Russian Federation, 630047, Russia, Novosibirsk, Zalesskogo, 6

Ekaterina A. Pashkina

Federal State Budgetary Scientific Institution, “Research Institute of Fundamental and Clinical Immunology” (RIFCI), Novosibirsk, Russia;
Novosibirsk State Medical University, Novosibirsk, Russia

Author for correspondence.
Email: pashkina.e.a@yandex.ru
ORCID iD: 0000-0002-4912-5512

PhD (Biology), Senior Researcher, Head, Laboratory of Immune Response Regulation, Associate Professor

Russian Federation, 630099 Russia, Novosibirsk, Yadrintsevskaya st.,14 630091, Russia, Novosibirsk, Krasny Prospekt, 52

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Copyright (c) Skachkov I.P., Aktanova A.A., Denisova V.V., Ushakova G.Y., Sizikova S.А., Pashkina E.A.

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