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

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.