Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy

Abstract

Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation. We also focus on the influence of immunosuppressive drugs on MDSCs as well as future obstacles and research directions in this field.

Keywords: Cell therapy; Immunology; Myeloid-derived suppressor cell (MDSC); Regulation; Transplantation.

Fig. 1

MDSC development and cell subsets in mice and humans. IMCs are part of the normal process of myelopoiesis. IMCs can differentiate into granulocytes, macrophages, and dendritic cells. However, IMCs can also differentiate into MDSCs, especially in some pathological conditions. MDSCs have two major subsets. In mice, G-MDSCs are defined as CD11b⁺Ly6C^lowLy6G⁺ cells, and M-MDSCs are defined as CD11b⁺Ly6C^highLy6G⁻ cells. In humans, G-MDSCs are characterized as CD11b⁺CD14⁻CD15⁺/CD11b⁺CD14⁻CD66⁺ cells, and M-MDSCs are defined as CD11b⁺CD14⁻CD15⁻/CD11b⁺CD14⁻CD66⁻ or CD11b⁺CD14⁺HLA⁻DR^low cells

Fig. 2

MDSC cell therapy. MDSCs from the bone marrow of recipients might be expanded in vitro and infused into allograft recipients. As immune suppressive innate immunocytes, MDSCs inhibit effector T cell (Teff) function. MDSCs might induce Tregs). The Teffs and Tregs migrate into draining lymph nodes and generate alloreactive Tregs. Alloreactive Tregs are further recruited to allografts where they inhibit rejection and induce tolerance