Myeloid-derived suppressor cells in multiple myeloma patients at the immune recovery and after high-dose chemotherapy and hematopoietic stem cell transplantation

Abstract

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.

Keywords

• multiple myeloma
• autologous hematopoietic stem cell transplantation
• time to disease progression
• myeloid-derived suppressor cells
• suppressor molecules
• arginase-1
• g-csf