EVALUATION OF GRANULOCYTE COLONY-STIMULATING FACTOR EFFECT ON THE EXPRESSION OF INHIBITORY RECEPTORS BY T CELLS IN MULTIPLE MYELOMA



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Abstract

AbstractAll types of immune cells are involved in the pathogenesis of multiple myeloma (MM). Granulocytic (G-MDSCs) and monocytic myeloid-derived suppressor cells (M-MDSCs) have significant protumor effects. The T-cell immune response may be reduced due to the development of T-cell exhaustion, characterized by the expression of inhibitory receptors PD-1, TIM-3, etc. Granulocyte colony-stimulating factor (G-CSF) supports the generation and expansion of MDSCs and can influence the functional properties of T cells. The purpose of our work was to investigate the possible effect of stimulation with G-CSF drugs on the induction of PD-1 and TIM-3 expression by T cells in patients with MM.

The study included 40 patients with MM who underwent mobilization of hematopoietic progenitor cells with G-CSF drugs (5 mcg/kg/day) for 4-5 days. Content of CD4+PD-1+, CD4+TIM-3+, CD8+PD-1+, CD8+TIM-3+ T cells, Lin-HLA-DR-CD33+CD66b+ G-MDSCs, CD14+HLA-DR- M-MDSCs was assessed before the start of a course of G-CSF injections (n=33), after a course of G-CSF on the first day of separation of hematopoietic progenitor cells (n=28) and after 3-6 months (n=40) by flow cytometry.

The relative content of G-MDSCs and M-MDSCs was significantly higher in patients with MM after a course of G-CSF. After 3-6 months the content of G-MDSCs and M-MDSCs decreased to the initial values. After the course of G-CSF, an increase in the content of CD4+PD-1+ T cells was noted compared to the values before the study. After 3-6 months, the content of this population did not differ from the initial values. The relative numbers of CD4+TIM-3+, CD8+PD-1+, CD8+TIM-3+ T cells did not change after a course of G-CSF. There were no significant correlations between the content of the populations of MDSCs and T cells expressing PD-1 and TIM-3 after a course of G-CSF.

Mobilization of hematopoietic stem cells by G-CSF in patients with MM is accompanied by a transient increase in MM populations and an isolated increase in CD4+PD-1+ T cells.

About the authors

Egor V. Batorov

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Email: ebatorov@mail.ru
ORCID iD: 0000-0003-2902-9336
SPIN-code: 6316-0759
Scopus Author ID: 35768879800
ResearcherId: L-8628-2015

Cand Sci (Med), seniour researcher

Russian Federation, 630099, г. Новосибирск, ул. Ядринцевская, д.14

Tatyana A. Aristova

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Email: taris06@mail.ru
ORCID iD: 0000-0002-4885-8327
Scopus Author ID: 57202359388

hematologist

Russian Federation, 630099, 14 Yadrintsevskaya St., Novosibirsk

Vera V. Denisova

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Email: verden@bk.ru
ORCID iD: 0000-0003-1951-2260
Scopus Author ID: 54881246800

PhD, head of Department of hematology and BMT, hematologist

630099, 14 Yadrintsevskaya St., Novosibirsk

Galina Yu. Ushakova

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Author for correspondence.
Email: bmt-novosibirsk@mail.ru
ORCID iD: 0000-0003-1822-6326
Scopus Author ID: 56528086500

PhD, hematologist

Russian Federation, 630099, 14 Yadrintsevskaya St., Novosibirsk

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Copyright (c) Batorov E.V., Aristova T.A., Denisova V.V., Ushakova G.Y.

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