scholarly journals Circulating CD 14 + 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

2016 ◽  
Vol 5 (7) ◽  
pp. 1654-1669 ◽  
Author(s):  
Jin Yin ◽  
Chunyan Wang ◽  
Min Huang ◽  
Xia Mao ◽  
Jianfeng Zhou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cellular Therapy ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Hla Dr ◽  
Clinical Potential

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation Mobilized With Pegylated Granulocyte Colony-Stimulating Factor Ameliorates Severe Acute Graft-Versus-Host Disease Through Enrichment of Monocytic Myeloid-Derived Suppressor Cells in the Graft: A Real World Experience

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Li ◽  
Jin Yin ◽  
Yun Li ◽  
Chunyan Wang ◽  
Xia Mao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

We compared the effectiveness and safety of pegylated granulocyte colony-stimulating factor (peg-G-CSF) vs. non-peg-G-CSF for hematopoietic stem cell mobilization in allogeneic hematopoietic stem cell transplantation in a real-world setting. We included 136 consecutive healthy donors treated with non–peg-G-CSF (n = 53) or peg-G-CSF (n = 83), and 125 consecutive recipients (n = 42 and 83, respectively) in this study. All harvesting was completed successfully. No significant difference in leukapheresis number and adverse events frequency was observed, nor were there severe adverse events leading to discontinuation of mobilization. The leukapheresis products mobilized by peg-G-CSF had higher total nucleated cells (p < 0.001), monocytic myeloid-derived suppressor cells (p < 0.001), granulocytic myeloid-derived suppressor cells (p = 0.004) and B cells (p = 0.019). CD34+ cells and other lymphocyte subsets (T cells, regulatory T cells, natural killer [NK] cells, etc.) were similar in both apheresis products. Patients who received grafts mobilized by peg-G-CSF exhibited a lower incidence of grade III-IV acute graft-versus-host disease (p = 0.001). The 1-year cumulative incidence of chronic graft-versus-host disease and relapse, 1-year probability of graft-versus-host disease-free relapse-free survival, and overall survival did not differ significantly between subgroups. Our results suggest that collecting allogeneic stem cells after the administration of peg-G-CSF is feasible and safe. Peg-G-CSF mobilized grafts may reduce severe acute graft-versus-host disease compared with non-peg-G-CSF mobilized grafts after allogeneic stem cell transplantation. The beneficial effects of a peg-G-CSF graft might be mediated by increased numbers of monocytic myeloid-derived suppressor cells.

Dynamic Change and Impact of Circulating Myeloid-Derived Suppressor Cells in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5472-5472
Author(s):  
Jin Yin ◽  
Yicheng Zhang
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Dynamic Changes ◽  
Hematopoietic Stem ◽  
Hla Dr ◽  
Tnf Α ◽  
Normal Controls

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population involved in tumor-associated immunosuppression and played immune regulatory roles in malignancies, infectious disease, autoimmune disease, trauma and inflammatory disease. Based on the significant suppressive functions, MDSCs raises great interests in the field of allogenetic hematopoietic stem cell transplantation (allo-HSCT) and graft-versus-host disease (GVHD). In recent years, studies described the immunosuppressive functions of CD14+HLA-DR-/low MDSCs, one of the few well-characterized MDSC subsets in human. However, the studies in patients with allo-HSCT are still scanty. This study identified the phenotype of CD14+HLA-DR-/low MDSCs and systematically monitored the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo-HSCT in order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes. We also detected the frequencies of other cell types and concentrations of relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long-term survival without influence on risk of recurrence after allo-HSCT. However, the level of MDSCs in the graft had more favorable predictive abilities compared with that in PBMCs when engraftment. Furthermore, MDSCs frequencies were significantly increased in patients developing aGVHD after allo-HSCT. In the patients with mild aGVHD (0-2), MDSCs accumulated at the time of engraftment after allo-HSCT and decreased to basal levels at about 4 weeks. MDSCs frequencies would keep in stable levels with slight fluctuations in the following weeks. But, in patients with severe aGVHD (3-4), MDSCs elevated slightly when engraftment. When aGVHD occurred, MDSCs frequencies would significantly increase. And a synchronized reduction of the levels of MDSCs was observed after effective management of aGVHD with immunosuppressive therapy. Besides, the levels of IL-10, IL-6, TNF-α, Arg-1, iNOS and HO-1 increased greatly both in patients with aGVHD and in high MDSCs group. It is speculated that MDSC accumulation at the onset of aGVHD might be caused by secondary inflammatory response, especially related to high concentrations of IL-6 and TNF-α. But the accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse in future. Overall, we suggested that MDSCs might be considered as a potential new approaches to regulate transplant rejection and achieve the recipient host long-term acceptance and survival. Figure 1. Frequencies of cell subsets in the graft. Frequencies of MDSCs in the graft were compared between normal controls and patients grouped by aGVHD (i) and aGVHD scores Figure 1. Frequencies of cell subsets in the graft. Frequencies of MDSCs in the graft were compared between normal controls and patients grouped by aGVHD (i) and aGVHD scores Figure 2. Increased frequencies of MDSCs in PBMCs of patients after allo-HSCT. (A) At the time of engraftment, the levels of MDSCs in PBMCs were compared between patients and normal controls (i), and were further analyzed according to aGVHD scores (ii). (B) After allo-HSCT, comparisons of MDSCs frequencies were performed between patients and normal controls grouped by aGVHD (i) and aGVHD severity (ii). (C) The dynamic changes of MDSCs frequencies after allo-HSCT were monitored in patients with aGVHD (i) and were analyzed based on aGVHD scores (ii). (D) The systematic monitoring of MDSCs frequencies was performed in all patients during the first 100 days after allo-HSCT grouped by aGVHD scores (i) and aGVHD severity (ii). Figure 2. Increased frequencies of MDSCs in PBMCs of patients after allo-HSCT. (A) At the time of engraftment, the levels of MDSCs in PBMCs were compared between patients and normal controls (i), and were further analyzed according to aGVHD scores (ii). (B) After allo-HSCT, comparisons of MDSCs frequencies were performed between patients and normal controls grouped by aGVHD (i) and aGVHD severity (ii). (C) The dynamic changes of MDSCs frequencies after allo-HSCT were monitored in patients with aGVHD (i) and were analyzed based on aGVHD scores (ii). (D) The systematic monitoring of MDSCs frequencies was performed in all patients during the first 100 days after allo-HSCT grouped by aGVHD scores (i) and aGVHD severity (ii). Disclosures No relevant conflicts of interest to declare.

scholarly journals Kinetics of Myeloid-Derived Suppressor Cells during Stem Cell Mobilization and Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2065-2065
Author(s):  
Anika Betsch ◽  
Omer Rutgeerts ◽  
Sabine Fevery ◽  
Ben Sprangers ◽  
Daan Dierickx ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Kinetics Of

Abstract Introduction: Myeloid-derived suppressor cells (MDSC) are immunosuppressive immature cells of the myeloid lineage that play a role in cancer induction, progression and immune evasion. Two major subtypes of MDSC can be distinguished: the polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC). Immune reconstitution after autologous hematopoietic stem cell transplantation (ASCT) may play a role in the therapeutic effect of ASCT in multiple myeloma (MM) and lymphoma patients. Since MDSC are immunosuppressive cells, we postulate they might play a role in the immune reconstitution following ASCT. Here, we studied the effect of G-CSF mobilization on MDSC accumulation and the kinetics of MDSC during G-CSF mobilization and ASCT in MM and lymphoma patients. Methods: Flow cytometry was used to measure MDSC in the stem cell graft (SCG) and peripheral blood mononuclear cells (PBMC) of 9 MM and 4 aggressive lymphoma patients. PMN-MDSC were defined as CD11b+ CD33dim HLA-DR- CD15+ cells and M-MDSC as CD11b+ CD33+ HLA-DRlow/- CD14+ cells. MDSC were measured at G-CSF start, time of stem cell (SC) collection and following ASCT at predefined time points (day 0, day +14, day +28, day +100, day +360). Values are reported as mean percentage of MDSC of living cells. For SC mobilization, MM patients received high-dose cyclophosphamide and G-CSF, lymphoma patients received R-DHAP and G-CSF. 3/9 MM patients and 4/4 lymphoma patients had a complete response at the time of SC collection. As conditioning regimen MM patients received melphalan, lymphoma patients received BEAM. Results: In PBMC of both MM and lymphoma patients, G-CSF mobilization increased PMN-MDSC levels: 10.06% at start G-CSF vs 46.44% at SC collection in MM patients (p=0.0006); 19.65% at start G-CSF vs 50.74% at SC collection in lymphoma patients (p=0.1143). After ASCT, PMN-MDSC levels tended to decrease: 28.21% at day 0 vs 7.94% at day +180 in MM patients (p=0.1061); 40.35% at day 0 vs 2.32% at day +180 (p=0.2000) in lymphoma patients. This in contrast to M-MDSC levels, which were not influenced by the use of G-CSF: 5.77% at start G-CSF vs 3.67% at SC collection in MM patients (p=0.3704); 6.52% at start G-CSF vs 3.23% at SC collection in lymphoma patients (p=0.3429). M-MDSC levels remained rather stable during the transplant period, but tended to increase after ASCT: 3.80% at day 0 vs 8.81% at day +180 in MM patients (p=0.0417); 1.24% at day 0 vs 16.70% at day +180 in lymphoma patients (p=0.3333). When comparing MDSC levels in PBMC and the SCG, we observed a decrease in the PMN-MDSC/M-MDSC ratio in the SCG in MM patients (p=0.0078) and in lymphoma patients (p=0.1250). In the SCG, fewer PMN-MDSC and more M-MDSC were present as compared to PBMC. Interestingly, the expression of IL-4Rα on PMN-MDSC (p=0.0078) and M-MDSC (p=0.0078) in PBMC was increased after G-CSF, at time of SC collection. Conclusion: The kinetics of both MDSC subtypes were comparable between MM and lymphoma patients. G-CSF mobilization resulted in the accumulation of PMN-MDSC, but not of M-MDSC. In addition, the expression of IL-4Rα increased on both MDSC subtypes after G-CSF, indicating a potential higher immunosuppressive capacity of MDSC. In both MM and lymphoma patients, PMN-MDSC levels decreased after ASCT, whereas M-MDSC levels increased after ASCT. This might be due to the natural development of these cells. However, further research, including the effect of MDSC on immune reconstitution and the effect of G-CSF on the immunosuppressive capacity of MDSC, is warranted. Disclosures No relevant conflicts of interest to declare.

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