The role of CD14+ HLA-DR-/low MDSC in aGVHD development after allogeneic hematopoietic stem cell transplantation / 中华器官移植杂志

ABSTRACT

Objective In order to evaluate the possible effects of myeloid-derived suppressor cells (MDSCs) on graft versus host disease (aGVHD) development and clinical outcomes,this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Peripheral blood was obtained from 30 patients and 10 healthy volunteers with heparin anticoagulant tubes for 6 mL.For patients,peripheral blood was collected during the first 100 days after allo-HSCT and MDSCs levels were detected by flow cytometry.For measuring the serum concentrations of IL-6,IL-10,IL-1β,TNF-α,Arg-1,HO-1 and iNOS,samples were analyzed using ELISA kits.Results Patients developing aGVHD were infused with significantly less number of MDSCs [(39.94 ± 8.383) 106/kg]than in those not developing aGVHD [(209.0 ± 57.68) 106/kg,P =0.002 6];Patients developing aGVHD Ⅰ-Ⅱ and patients without aGVHD received significantly greater number of MDSCs [(61.96 ± 13.67) 106/kg and (209.0 ± 57.68) 106/kg] than in those developing aGVHD Ⅲ-Ⅳ [(20.37 ±4.304) 106/kg,P =0.013 9].After allo-HSCT,the mean percentage of MDSCs increased markedly in patients developing aGVHD [(7.725 ± 1.460)％] as compared with those not developing aGVHD [(3.423± 1.044)％,P =0.021 3].The high MDSCs group (＞53.712 × 106/kg) showed more favorable clinical outcomes than in the low MDSCs group (≤53.712 × 106/kg).The 2-year overall survival rate as 100％ in high MDSCs group,and 50％ in low MDSCs group (P =0.001 3).The cumulative incidence of 2-year relapse was 6.250％ and 29.252％ in high MDSCs group and low MDSCs group respectively (P =0.112 3).The cumulative incidence of NRM was significantly lower in high MDSCs group (0％) than in low MDSCs group (49.519％,P=0.001 8).MDSCs frequencies significantly increased in patients developing aGVHD after allo-HSCT.After allo-HSCT,the concentrations of IL-6,IL-10,TNF-α,Arg-1,iNOS and HO-1 were significantly elevated in patients developing aGVHD.Conclusion The number of MDSCs when engraftment may be used as a predictor for the development and severity of aGVHD.MDSCs might be considered as a potential new approach to regulate transplant rejection and achieve long-term survival.