title: 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.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Lv
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Kong
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D042381:Granulocyte Precursor Cells / Q000276:immunology* / Q000637:transplantation; D006239:Haplotypes; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D007938:Leukemia / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000637:transplantation; D015999:Multivariate Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D016179:Granulocyte Colony-Stimulating Factor