Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation
Introduction. Myeloid-derived suppressor cells (MDSCs) play an important role in restriction of the immune response and are associated with a poor prognosis in cancer. Mobilization of hematopoietic stem cells (HSCs) before high-dose chemotherapy (HCT) with autologous HSC transplantation (auto-HSCT)...
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Tomsk National Research Medical Center
2023-01-01
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| Series: | Сибирский онкологический журнал |
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| Online Access: | https://www.siboncoj.ru/jour/article/view/2372 |
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| author | T. V. Tyrinova E. V. Batorov T. A. Aristova G. Yu. Ushakova S. A. Sizikova V. V. Denisova A. A. Ostanin E. R. Chernykh |
| author_facet | T. V. Tyrinova E. V. Batorov T. A. Aristova G. Yu. Ushakova S. A. Sizikova V. V. Denisova A. A. Ostanin E. R. Chernykh |
| author_sort | T. V. Tyrinova |
| collection | DOAJ |
| description | Introduction. Myeloid-derived suppressor cells (MDSCs) play an important role in restriction of the immune response and are associated with a poor prognosis in cancer. Mobilization of hematopoietic stem cells (HSCs) before high-dose chemotherapy (HCT) with autologous HSC transplantation (auto-HSCT) is accompanied by a signifcant increase in MDSC counts in peripheral blood and apheresis product of multiple myeloma (MM) patients. However, quantitative changes of these cells at the post-transplant and their role at the immune recovery remain unexplored.The study was aimed to analyze the dynamics of circulating MDSC counts and the expression of suppressor molecule arginase-1 in patients with MM in the frst 12 months after HCT and auto-HSCT and evaluate association between MDSCs and transplantation outcomes.Material and Methods. The study included 44 MM patients who underwent HCT and auto-HSCT. The relative number of granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), and early-stage MDSCs (E-MDSCs), as well as the expression of arginase-1 in each of MDSC subsets was evaluated by fow cytometry in patient peripheral blood samples.Results. At the engraftment (day +12 – +16, leukocytes >1×109 /l), M-MDSC relative count was increased (pU=0.038), as well as the relative (pU=0.003) and absolute (pU˂0.0001) counts of G-MDSCs, decreasing after 6 months down to pre-transplant values (рU=0.007, рU=0.024 and рU=0.02, respectively) and remaining at the same level at the 12-month follow-up period. The absolute count of E-MDSCs by the time of the engraftment decreased transiently (pU=0.004 vs before HCT), gradually recovering by 12-month follow-up (pU=0.032 vs day +12 – +16). The remission within 12 months in the group with G-MDSCs˂0.17 % at the engraftment was observed in 67 ± 11 % of patients, with G-MDSCs >0.17 % – in 94 ± 6 % of patients (p=0.049). During the 12-month post-transplant, the number of M-MDSCs expressing arginase-1 has been increasing, with a tendency to lower values at the engraftment in patients with early MM relapse (pU=0.09).Conclusion. The association of early MM relapse after auto-HSCT with the lower count of G-MDSCs and the lower count of arginase-1+ M-MDSCs at the engraftment suggests that MDSCs is involved in the restriction of homeostatic proliferation as a factor for more effective immune recovery. |
| first_indexed | 2024-04-10T01:51:42Z |
| format | Article |
| id | doaj.art-f997b6b5c6eb4cdeb587a6e6292886bc |
| institution | Directory Open Access Journal |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| last_indexed | 2025-03-14T10:07:19Z |
| publishDate | 2023-01-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj.art-f997b6b5c6eb4cdeb587a6e6292886bc2025-03-02T11:16:17ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682023-01-01216475810.21294/1814-4861-2022-21-6-47-581062Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantationT. V. Tyrinova0E. V. Batorov1T. A. Aristova2G. Yu. Ushakova3S. A. Sizikova4V. V. Denisova5A. A. Ostanin6E. R. Chernykh7Research Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyIntroduction. Myeloid-derived suppressor cells (MDSCs) play an important role in restriction of the immune response and are associated with a poor prognosis in cancer. Mobilization of hematopoietic stem cells (HSCs) before high-dose chemotherapy (HCT) with autologous HSC transplantation (auto-HSCT) is accompanied by a signifcant increase in MDSC counts in peripheral blood and apheresis product of multiple myeloma (MM) patients. However, quantitative changes of these cells at the post-transplant and their role at the immune recovery remain unexplored.The study was aimed to analyze the dynamics of circulating MDSC counts and the expression of suppressor molecule arginase-1 in patients with MM in the frst 12 months after HCT and auto-HSCT and evaluate association between MDSCs and transplantation outcomes.Material and Methods. The study included 44 MM patients who underwent HCT and auto-HSCT. The relative number of granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), and early-stage MDSCs (E-MDSCs), as well as the expression of arginase-1 in each of MDSC subsets was evaluated by fow cytometry in patient peripheral blood samples.Results. At the engraftment (day +12 – +16, leukocytes >1×109 /l), M-MDSC relative count was increased (pU=0.038), as well as the relative (pU=0.003) and absolute (pU˂0.0001) counts of G-MDSCs, decreasing after 6 months down to pre-transplant values (рU=0.007, рU=0.024 and рU=0.02, respectively) and remaining at the same level at the 12-month follow-up period. The absolute count of E-MDSCs by the time of the engraftment decreased transiently (pU=0.004 vs before HCT), gradually recovering by 12-month follow-up (pU=0.032 vs day +12 – +16). The remission within 12 months in the group with G-MDSCs˂0.17 % at the engraftment was observed in 67 ± 11 % of patients, with G-MDSCs >0.17 % – in 94 ± 6 % of patients (p=0.049). During the 12-month post-transplant, the number of M-MDSCs expressing arginase-1 has been increasing, with a tendency to lower values at the engraftment in patients with early MM relapse (pU=0.09).Conclusion. The association of early MM relapse after auto-HSCT with the lower count of G-MDSCs and the lower count of arginase-1+ M-MDSCs at the engraftment suggests that MDSCs is involved in the restriction of homeostatic proliferation as a factor for more effective immune recovery.https://www.siboncoj.ru/jour/article/view/2372multiple myelomaautologous hematopoietic stem cell transplantationtime to disease progressionmyeloid-derived suppressor cellssuppressor moleculesarginase-1g-csf |
| spellingShingle | T. V. Tyrinova E. V. Batorov T. A. Aristova G. Yu. Ushakova S. A. Sizikova V. V. Denisova A. A. Ostanin E. R. Chernykh Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation Сибирский онкологический журнал multiple myeloma autologous hematopoietic stem cell transplantation time to disease progression myeloid-derived suppressor cells suppressor molecules arginase-1 g-csf |
| title | Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation |
| title_full | Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation |
| title_fullStr | Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation |
| title_full_unstemmed | Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation |
| title_short | Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation |
| title_sort | myeloid derived suppressor cells in multiple myeloma patients at the immune recovery and after high dose chemotherapy and hematopoietic stem cell transplantation |
| topic | multiple myeloma autologous hematopoietic stem cell transplantation time to disease progression myeloid-derived suppressor cells suppressor molecules arginase-1 g-csf |
| url | https://www.siboncoj.ru/jour/article/view/2372 |
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