Monocytic and promyelocytic myeloid‐derived suppressor cells may contribute to G‐CSF‐induced immune tolerance in haplo‐identical allogeneic hematopoietic stem cell transplantation

Abstract

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on monocytic (M), promyelocytic (P), and granulocytic (G) myeloid-derived suppressor cells (MDSCs) both in bone marrow and peripheral blood of 20 healthy donors and the association of MDSCs subgroups with acute and chronic graft-versus-host disease (aGvHD/cGvHD) in 62 patients who underwent haplo-identical allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who received a higher absolute counts of M-MDSCs or P-MDSCs exhibited lower incidence of grade II-IV aGvHD (P = 0.001; P = 0.031) and extensive cGvHD (P = 0.011; P = 0.021). In the multivariate analysis, absolute counts of MDSCs in allografts emerged as independent factors that reduced the occurrence of grade II-IV aGvHD (M-MDSCs: HR = 0.087, 95% CI = 0.020-0.381, P = 0.001; P-MDSCs: HR = 0.357, 95% CI = 0.139-0.922, P = 0.033) and extensive cGvHD (M-MDSCs: HR = 0.196, 95% CI = 0.043-0.894, P = 0.035; P-MDSCs: HR = 0.257, 95% CI = 0.070-0.942, P = 0.04). Delayed M-MDSC reconstitution was associated with aGvHD onset. The 3-year cumulative incidence of transplant related mortality and relapse, 3-year probability of disease-free survival, and overall survival did not differ significantly between these subgroups. Our results suggested that G-CSF-induced immune tolerance may be mediated by M/P-MDSCs in allo-HSCT.

Circulating CD14+HLA‐DR‐/low myeloid‐derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft‐versus‐host disease

“…These findings were in line with that reported by Vendramin A and Lv M et al. very recently . Both of the studies demonstrated the positive effects of high levels of MDSCs in the graft.…”

Functional Myeloid-Derived Suppressor Cell Subsets Recover Rapidly after Allogeneic Hematopoietic Stem/Progenitor Cell Transplantation

“…At other time points, M-MDSC recovery or G-MDSC recovery was not associated with GVHD. This differs from a very recent report in which acute GVHD patients had lower percentages of M-MDSCs at day þ15 but higher percentages of M-MDSCs at day þ30 compared with nonacute GVHD patients [25]. Interestingly, in the present study, where G-MDSC number recovered to normal range at days 27 to 29, the ratio of G-MDSC at days 27 to 29-to-G-MDSC at preconditioning baseline (G-MDSCR) might correlate with the incidence of GVHD ( Figure 5B).…”

Mature CD10+ and immature CD10− neutrophils present in G-CSF–treated donors display opposite effects on T cells

“…In this context, there is currently an increasing interest in clarifying the role of immunosuppressive myeloid cell populations in patients undergoing unrelated donor allogeneic stem cell transplantation, for the final purpose of preventing the occurrence of acute graft-versus-host disease. [62][63][64] In this regard, our work encourages prospective studies aimed at carefully investigating the frequencies of mature CD66b populations isolated from patients with inflammatory diseases other than GDs display opposite effects on T-cell functions are eagerly awaited. Finally, considering the interest in CD10 as a prognostic/ diagnostic marker in oncology, 65 particularly on the correlation …”