Granulocytic and Monocytic Myeloid-Derived Suppressor Cells May Have Different Role on Allogeneic Stem Cell Transplant Outcomes

Background: Myeloid-derived suppressor cells (MDSC), a heterogeneous group of myeloid cells, have emerged as immune regulators, having a high potential to suppress T cell responses. Although uniform characterization of human MDSC needs to be elucidated, they can be divided into the categories of granulocytic (G-MDSC) and monocytic (M-MDSC). Recent studies have reported that MDSC, generated in vitro or in vivo, alleviated the severity of graft-versus-host disease (GVHD) in murine allogeneic transplant models and in human delayed M-MDSC reconstitution was associated with the occurrence of acute GVHD. However, whether G-MDSC and M-MDSC may have different role on the outcomes after allogeneic stem cell transplantation (SCT) remains obscure.

Methods: This prospective study was aimed to identify the clinical implications of early G-MDSC and M-MDSC expansion as a predictor for the occurrence of acute GVHD (aGVHD), infections, CMV reactivation, and survival outcomes after allogeneic SCT. The peripheral blood samples from 130 patients with acute myeloid leukemia and myelodysplastic syndrome-refractory anemia with excess blasts, who underwent allogeneic SCT between Jan. 2013 through Oct. 2014 were taken at engraftment and analyzed by flow cytometry.

Results: Seventy-eight men and 52 women were enrolled in this study. The median age was 45.5 years (range, 17-68). To compare the predictive role of MDSC for various transplants, the patients were grouped according to the median values of the frequency of G-MDSC and M-MDSC. High G-MDSC at engraftment was a potential factor promoting the occurrence of ≥ grade 2 aGVHD at 100 days (30.8% vs. 47.7%, P = 0.023), whereas high M-MDSC group had no difference in the occurrence of ≥ grade 2 GVHD compared that of low M-MDSC group. There was no difference in CMV reactivation, infection rate, and TRM according to G-MDSC recovery. In contrast, patients in the high M-MDSC group had a higher cumulative incidence of infection at 100 days (25.1% vs. 48.2%, P = 0.002), and TRM (6.4% vs. 22.6%, P = 0.018), compared with the patients in the low group. Ultimately, multivariate analyses reveal that high G-MDSC had a trend for the occurrence of ≥ grade 2 GVHD at 100 days (RR 1.72, 95%CI (0.95-3.11), P = 0.071) and high M-MDSC could predict a higher infection rate (RR 2.30, 95%CI (1.30-4.07), P = 0.004) and higher transplant related mortality (TRM) (RR 3.30, 95%CI (1.10-9.90), P = 0.033). In addition, high M-MDSC was associated lower event-free survival (P = 0.008).

Conclusion: Our data demonstrated that the high G-MDSC in the peripheral blood at engraftment was associated with a trend toward higher incidence of aGVHD and high M-MDSC was an independent factor for infection and TRM. Discrepancy of the role of G-MDSC and M-MDSC after allogeneic SCT suggests that difference of MDSC reconstitution into the more differentiated subset may predict transplant outcomes, including aGVHD, infections, and TRM.