Early myeloid-derived suppressor cells (HLA-DR−/lowCD33+CD16−) expanded by granulocyte colony-stimulating factor prevent acute graft-versus-host disease (GVHD) in humanized mouse and might contribute to lower GVHD in patients post allo-HSCT

Abstract

IntroductionMyeloid-derived suppressor cells (MDSCs) are proposed to control graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the definition of human MDSCs has not yet reached consensus, and the mechanism of MDSCs to control GVHD remains unclear.MethodsImmature myeloid cells (HLA-DR−/lowCD33+CD16−) were tested before and after granulocyte colony-stimulating factor (G-CSF) administration in healthy donor and isolated for suppression assays and co-culture with T cells in vitro. Isolated cells were infused in humanized mice for a xenogeneic model of acute GVHD. One hundred allo-HSCT recipients were enrolled prospectively to assess the role of HLA-DR−/lowCD33+CD16− cells in grafts on the occurrence of acute GVHD.ResultsIn the present study, G-CSF mobilized HLA-DR−/lowCD33+CD16− cells with immunosuppressive properties in donor peripheral blood. These cells contained more interleukin-10+ and transforming growth factor-beta (TGF-β)+ cells after G-CSF administration and inhibited the proliferation of autologous donor T cells in a TGF-β-dependent manner. Meanwhile, these immature myeloid cells promoted regulatory T cell expansion and induced Th2 differentiation. Importantly, these cells prevented acute GVHD in a humanized mouse model. Moreover, clinical cohort results showed that the number of HLA-DR−/lowCD33+CD16− cells in the donor graft was the only independent risk factor inversely correlated with the incidence of grade II–IV acute GVHD in the recipients (HR 0.388, 95% CI 0.158–0.954, p = 0.039).ConclusionHLA-DR−/lowCD33+CD16− cells represent functional MDSCs that may control acute GVHD in allo-HSCT.Electronic supplementary materialThe online version of this article (10.1186/s13045-019-0710-0) contains supplementary material, which is available to authorized users.

Myeloid-derived suppressor cells in hematological malignancies: friends or foes

“…Fan demonstrated that a higher frequency of MDSCs (Lin low/neg HLA-DR − CD33 + CD11b + ) in the G-CSF primed BM than in the G-CSF peripheral blood stem cells harvest (G-PBSC) grafts lead to a better GVHD and relapse-free survival (GRFS) and less GVHD [65]. Wang identified a new subset of eMDSCs (HLA-DR−/lowCD33 + CD16- cells) in a humanized mice model that may control acute GVHD in mice HSCT, and these cells were also identified as an independent factor that reduced the occurrence of grade II-IV aGvHD in allo-HSCT patients [66]. Schneidawind reported that administration of G-CSF- donor lymphocyte infusion (DLI) results in graft-versus-leukemia effects without exacerbating GVHD because of the M-MDSCs in the DLI component [67].…”

Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host diseas with combination of regulatory T cells

“…In recent studies, MDSCs have potential for the treatment of GVHD [16,17,34]. However, our data show that MDSCs alone had low clinical e cacy.…”

Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells

“…In recent studies, MDSCs have potential for the treatment of GVHD [ 16 , 17 , 34 ]. However, our data show that MDSCs alone had low clinical efficacy.…”