Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the recipient, after allo-HSCT) might mediate immune suppression through multiple mechanisms. However, it remains unclear how MDSCs can be distinguished from their normal myeloid counterparts in the hematopoietic stem cell donor graft and during immune reconstitution after allo-HSCT in the recipient. Our ability to understand their exact role in allo-HSCT is limited by the absence of a specific gene signature or surface markers for identifying MDSCs among myeloid cells and by their plasticity in different microenvironments. According to various studies, MDSCs might induce transplant tolerance and control graft vs. host disease (GVHD), but their impact on the graft vs. tumor effect (GVT) is not fully understood. In fact, we know that MDSCs commonly expand in patients with cancer, and they are thought to promote hematological malignancy progression. However, little is known about whether depleting them might be an effective strategy for enhancing GVT effects. Here, we review data published over the past 40 years on allo-HSCT to delineate the different MDSC subsets, and their abilities to induce transplant tolerance and preserve the GVT effect. This review will provide a basis for determining whether one MDSC subset might be proposed as the most appropriate candidate for cellular therapies, due to its ability to modulate GVHD.

Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation

“…A higher presence of Tregs was also reported in those patients (50). Other studies suggest alternative mechanisms such as a strengthened crosstalk between MDSCs and Tregs or NKT cells (28,51). In agreement with these studies, an increase of the myeloid cell compartment was also observed at day 28 post-HCT after treatment with UnLicNK cells, but an increase on CD4 T cells or NKT cells was not observed at this time point in the organs analyzed.…”

The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative

“…The traditional classification of myeloid cells in the periphery and MDSC at the tumor site have recently been revised using several modern technologies, aiming at categorizing single cells based on their gene signature (single-cell RNAseq) and expression of cell surface receptors and some intracellular proteins (mass cytometry, CyTOF). The basic hypothesis is that, beyond the variety between human and mouse in the classification of these cells (24), in each species, the gene signature and cell surface protein expression may vary depending on the organ from which cells are isolated (BM, spleen, blood, LNs, tumor site) and may also differ between tumor types (122)(123)(124)(125)(126). These studies are still in early development but may pave a new direction in scientific research and its translational implications.…”

The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD)

“…Generating MDSCs from human is difficult due to low concentration. More than one month of cultivation is required to produce sufficient MDSCs which might be too long for their application as a treatment for severe acute GVHD, whereas the ideal method for their processing has not yet been identified [ 91 ].…”