Association Between MDSCs and Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation,
Authors: Liu Qifa , Ling Yiwen , Fan Zhiping , Zhang Yu , Huang Fen , Wu Xiuli , Xuan Li , Wu Meiqing 
Published: October 2019

Abstract
Abstract 4069
Myeloid derived suppressor cells (MDSCs) are a group of heterogeneous cells, derived from bone marrow progenitor cells and immature myeloid cells. In tumor development and progression, MDSCs play a role of immunosuppressive effect. Recently, researchers found that granulocyte colony-stimulating factor (G-CSF) could mobilize MDSCs from bone marrow (BM) to peripheral blood (PB), but there is unknown about the effect of G-CSF to MDSCs in the human body and the relationship between MDSCs and graft-verse-host disease (GVHD). So we investigated the association between MDSCs and acute graft-verse-host disease (aGVHD).
The expression of MDSCs and adhesion molecules in the BM, PB and peripheral blood stem cell grafts in 30 related donors, were detected by flow cytometry before and after recombined human G-CSF (rhG-CSF) mobilization. The expression of arginase (ARG) and inducible nitric oxide synthase (iNOS) were detected by enzyme-linked immunosorbent assay. According to the median number of MDSCs in peripheral blood stem cell harvests (9.60×106/kg), 30 leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were divided into two groups, high MDSCs group and low MDSCs group. The hematopoietic/immune reconstitution, incidence of aGVHD, relapse, and survival rate were compared between two groups.
MDSCs could be detected in the blood and BM in healthy donors, the proportion in nuclear cells in the blood and BM was 0.30% ± 0.09% and 0.53% ± 0.16%, respectively. MDSCs in BM was higher than that in PB (P <0.001). After 5 days of rhG-CSF mobilization, the proportion in the blood and BM was 0.66% ± 0.28% and 0.72% ± 0.13%, respectively. The difference between proportion in the blood before and after mobilization was significant (P =0.017). Adhesion molecules on MDSCs surface after rhG-CSF mobilization were significant lower than that before rhG-CSF mobilization, both in blood and BM (P <0.001). The expression of ARG and iNOS after mobilization were significantly higher than that before mobilization (P<0.001), but not in BM (P =0.695, 0.073). There was a significant negative correlation between the number of transplanted MDSCs cells and the grading of aGVHD (correlation coefficient rs =0.445, P =0.014). The difference between the incidence of aGVHD in high MDSCs group and low MDSCs group (20.00% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(315\) \end{document} vs 66.67% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(1015\) \end{document}, P =0.011), there was no significant difference between the hematopoietic/immune reconstitution, relapse rate (26.67% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(415\) \end{document} vs 20.00% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(315\) \end{document}, P =0.671) and disease-free survival rate (46.7% ±14.2% vs 38.9%±15.8%, P =0.833) in two groups.
In conclusion, in the human body, rhG-CSF could transfer more MDSCs from BM into the blood. RhG-CSF mobilization could increase the number of MDSCs in graft, which may be related to low incidence of aGVHD after allo-HSCT. The mechanism of rhG-CSF mobilized MDSCs to blood may be related to adhesion factor on MDSCs surface. The incidence of aGVHD in patients who accepted high MDSCs cells was lower; there was a significantly negative correlation between MDSCs transplant value and the grading of aGVHD. MDSCs cell infusion did not affect the function of immune reconstitution and the effect of graft versus leukemia.

Disclosures:
Liu: National Natural Science Foundation of China (No.30971300), Science and Technology Planning Project of Guangdong Province of China (No.2009A030200007): Research Funding.