Myeloidderived peripheral blood suppressor cells at haematopoietic stem cell mobilisation in multiple myeloma patients
T. A. Aristova,
E. V. Batorov,
V. V. Sergeevicheva,
S. A. Sizikova,
G. Yu. Ushakova,
A. V. Gilevich,
E. Ya. Shevela,
A. A. Ostanin,
E. R. Chernykh https://doi.org/10.35754/0234-5730-2021-66-2-218-230
Abstract
Introduction. Multiple myeloma (MM) is a B-cell malignancy with clonal expansion of plasma cells in bone marrow. Highdose chemotherapy with autologous haematopoietic stem cell transplantation is among main consolidation therapies in MM. Myeloid-derived suppressor cells (MDSCs) are immature myeloid-accompanying cells able to suppress the immune response. The administration of granulocyte colony stimulating factor (G-CSF) to mobilise haematopoietic stem cells (HSCs) increases the MDSC count in peripheral blood (PB).
Aim — to study MDSC subsets in PB of remission MM patients and their incidence dynamics at HSC mobilisation.
Methods. The study surveyed 35 MM patients prior to and after HSC mobilisation. The counts of granulocytic (G-MDSCs; Lin–HLA-DR–CD33+ CD66b+), monocytic (М-MDSCs; CD14+ HLA-DRlow/–) and early MDSCs (E-MDSCs; Lin–HLA-DR– CD33+ CD66b–) were estimated in flow cytometry.
Results. Remission MM patients differed from healthy donors in higher relative counts of G-MDSCs (Lin–HLA-DR– CD33+ CD66b+) and increased relative and absolute counts of М-MDSCs (CD14+ HLA-DRlow/–). М-MDSCs significantly outnumbered G-MDSCs. MDSC subset counts were elevated in complete response (CR) and very good partial response (VGPR), as well as in partial response (PR). Higher relative MDSC counts were associated with greater pretreatment (2–3 lines of chemotherapy). After HSC mobilisation with cyclophosphamide 2–4 g/m2 + G-CSF (filgrastim 5 μg/kg/day), the median relative E-MDSC and M-MDSC counts increased by 2.3 and 2.0 times, respectively, while the relative G-MDSC count raised 46-fold perturbing the MDSC subset balance.
Conclusion. Remission MM patients had the increased relative G-MDSC and both relative and absolute M-MDSC counts compared to donors. A greater patient pretreatment was associated with higher relative G-MDSC counts. Treatment response (CR/VGPR vs. PR) was not coupled with MDSC count variation. The G-CSF-induced HSC mobilisation entailed a significant expansion of all three MDSC subsets in PB.
Keywords
Supporting agencies: Research was supported by the Russian Foundation for Basic Research (grant 20-15-00357 a)
About the Authors
T. A. Aristova
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Tatiana A. Aristova, Physician (haematology), Department of Haematology with Bone Marrow Transplantation Unit
630099, Novosibirsk
E. V. Batorov
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Egor V. Batorov, Cand. Sci. (Med.), Researcher, Laboratory of Cell Immunotherapy
630099, Novosibirsk
V. V. Sergeevicheva
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Vera V. Sergeevicheva, Cand. Sci. (Med.), Head of the Department of Haematology with Bone Marrow Transplantation Unit
630099, Novosibirsk
S. A. Sizikova
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Svetlana A. Sizikova, Cand. Sci. (Med.), Physician (haematology), Department of Haematology with Bone Marrow Transplantation Unit
630099, Novosibirsk
G. Yu. Ushakova
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Galina Yu. Ushakova, Cand. Sci. (Med.), Physician (haematology), Department of Haematology with Bone Marrow Transplantation Unit
630099, Novosibirsk
A. V. Gilevich
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Andrey V. Gilevich, Cand. Sci. (Med.), Head of the Department of Resuscitation and Intensive Care
630099, Novosibirsk
E. Ya. Shevela
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Ekaterina Ya. Shevela, Dr. Sci. (Med.), Leading Researcher, Laboratory of Cell Immunotherapy
630099, Novosibirsk
A. A. Ostanin
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Alexander A. Ostanin, Dr. Sci. (Med.), Professor, Chief Researcher, Laboratory of Cell Immunotherapy
630099, Novosibirsk
E. R. Chernykh
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
Elena R. Chernykh, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Cell Immunotherapy
630099, Novosibirsk
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For citations:
Aristova T.A., Batorov E.V., Sergeevicheva V.V., Sizikova S.A., Ushakova G.Yu., Gilevich A.V., Shevela E.Ya., Ostanin A.A., Chernykh E.R. Myeloidderived peripheral blood suppressor cells at haematopoietic stem cell mobilisation in multiple myeloma patients. Russian journal of hematology and transfusiology. 2021;66(2):218-230. (In Russ.) https://doi.org/10.35754/0234-5730-2021-66-2-218-230
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