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) is accompanied by a significant 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 first 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 flow 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 (puu=0.007, pu=0.024 and pu=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 % - 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.