scholarly journals Infusion of Autograft Natural Killer Cells/CD14 + hla-DR DIM Myeloid-Derived Suppressor Cells Ratio Predicts Survival in Non-Hodgkin Lymphoma Undergoing Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation (APHSCT)

2017 ◽  
Vol 23 (3) ◽  
pp. S84-S85 ◽  
Author(s):  
Ankit J. Kansagra ◽  
David J. Inwards ◽  
Stephen Ansell ◽  
Ivana N. Micallef ◽  
Patrick B. Johnston ◽  
...  
Keyword(s):  
Stem Cell ◽  
Natural Killer Cells ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Non Hodgkin Lymphoma ◽  
Hla Dr

Low Counts Of Natural Killer Cells CD56 bright CD16 negative After Engraftment Are Associated With Worse Survival In Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4625-4625
Author(s):  
Matheus Vescovi Gonçalves ◽  
Mihoko Yamamoto ◽  
Eliza Y. S. Kimura ◽  
Vergilio Antonio Renzi Colturato ◽  
Maura Valerio Ikoma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Natural Killer Cells ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Related Mortality

Background Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints. Objectives To evaluate the impact of NK subpopulations recovery on HSCT endpoints: relapse, GVHD, non-relapse mortality and overall survival. Patients and Methods NK (CD3-, CD56+) subpopulations (NK56++16- and NK56+16+) were quantified by multiparametric flow cytometry at 9 sequential time points (before conditioning, at engraftment, and at days 3, 7, 14, 21, 60, 100 and 180 after engraftment). Overall, 111 patients, from 4 HSCT centers (65% male, median age 17 years, range 1-74), receiving bone marrow (BM, 46%), umbilical cord (UCB, 32%) or peripheral blood (PB, 22%) from unrelated (n=90) or related donors (n=21) were studied. The most common diagnosis was acute leukemia (AML 36%, ALL 31%, MDS 9%, CML 9%, Aplastic anemia 8%). Most patients received myeloablative conditioning (MAC) regimens (60%). Antithymocyte globulin (ATG) was used in 44 patients (40%) and total body irradiation (TBI) in 56 (51%). Median follow up time was 14 months (range 4-35). Results Eighty-six patients presented sustained allogeneic recovery (no differences among sources). Of these, median time to neutrophil engraftment was 18 days (range: 8-52). The cumulative incidence (CI) of non-relapse-related mortality (NRM) was significantly higher in those with lower counts of NK56++16– during first 3 weeks after HSCT (34% at 1 year for patients with less than 30 cells/uL at day 21 vs 11% for patients with higher counts, p=0.03). Overall survival was significantly worse in patients with lower counts of NK56++16- subpopulations in the day 21 after engraftment (86% at 1 year vs 54% for patients with less than 30 cells/uL – p=0.003). CI of grade II-IV acute GVHD and relapse were not significantly affected by NK counts. The number of NK56+16+ cells did not affect any endpoint studied. Cell source, age and conditioning regimen did not affect any of the NK subpopulations counts. In multivariate analysis, NK56++16- counts lower than 30 cells/uL at 21 and 60 days after engraftment remain an independent risk factor for non relapse mortality [HR: 4.8, CI (95%): 1.2-18.8]. Conclusions Low NK56++16- counts in the first weeks after HSCT are associated with increased non relapse related mortality, but not acute GVHD or relapse. The mechanisms that rules the NK56++16- role on immunity deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

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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