Functional Myeloid-Derived Suppressor Cell Subsets Recover Rapidly after Allogeneic Hematopoietic Stem/Progenitor Cell Transplantation

Abstract

Myeloid-derived suppressor cells (MDSCs) are regulatory cell populations that have the ability to suppress effector T cell responses and promote the development of regulatory T cells (Tregs). They are a heterogeneous population of immature myeloid progenitors that include monocytic and granulocytic subsets. We postulated that given the rapid expansion of myeloid cells post-transplant, these members of the innate immune system may be important contributors to the early immune environment post-transplant. To evaluate the kinetics of recovery and function of MDSCs after allogeneic hematopoietic stem cell transplant (HSCT), 26 patients undergoing allogeneic HSCT were studied at 6 time points in the first 3 months after HSCT. Both MDSC subsets recovered between 2 and 4 weeks, well before the recovery of T and B lymphocytes. MDSC subset recovery positively correlated with T, B, and/or double-negative T cell numbers after HSCT. MDSCs isolated from patients post-transplant were functional in that they suppressed third-party CD4(+) T cell proliferation and Th1 differentiation and promoted Treg development. In conclusion, functional MDSC are present early after HSCT and likely contribute to the regulatory cell population post-transplant.

Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation

“…Nevertheless, as such, our results should be interpreted with some caution until they can be validated in a large independent cohort. We also recognize that circulating PBMCs fluctuate in the course of routine clinical practice, and thus conferring prognostic value to a single set of values in time needs to be interpreted cautiously; however, it is reassuring that our measurement time point was supported by analyses looking at MDSC recovery over time, in which both MDSC subsets recovered maximally between 2 and 4 weeks, well before the recovery of T and B lymphocytes [49].…”

Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia

“…Vendramin et al [14] reported that higher doses of monocytic MDSCs (M-MDSCs) in the G-PBSC grafts were associated with less aGVHD. Guan et al [36] reported that the number of G-MDSCs in PB of patients at the preconditioning time point was negatively correlated with aGVHD. As the cellular effectors of aGVHD are mainly cytotoxic T lymphocytes and natural killer cells [37, 38], MDSCs are able to inhibit alloreactive responses mediated by T lymphocytes and NK cells through a variety of mechanisms, including l -arginine depletion by arginase 1 and the inducible nitric oxidase (iNOS), generation of reactive oxygen species, release of transforming growth factor-beta (TGF-beta) and IL-10, cysteine sequestration, and regulatory T (Treg) cell induction [11, 39–41].…”

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

“…Finally, evidence that it is possible to identify immunosuppressive neutrophil populations directly within total leukocytes (obtained by a simple red cell lysis of blood without performing density gradient centrifugation) also exists. The latter immunosuppressive neutrophil populations have been, for instance, obtained from healthy volunteers administered with endotoxin, or from patients with severe injury , cancer , HIV‐1 infection , or undergoing allogeneic hematopoietic stem cell transplantation , or even from elderly individuals . Among these studies, Pillay et al .…”

“…To further highlight here how confusing is the nomenclature, even immunosuppressive neutrophils directly isolated from total leukocytes (e.g. not from the mononuclear cell fraction) have been recently defined as ‘G‐MDSCs’ !! Taken together, all these findings point to the necessity of carefully comparing immunosuppressive LDNs/G‐MDSCs with mature immunosuppressive neutrophils present within NDNs and/or total leukocytes from the same diseased individuals: such an analytical comparison will clarify whether phenotypic/functional changes are peculiar of specialized LDN populations or instead occur in all circulating neutrophils.…”