The Role of Myeloid-Derived Suppressor Cells in Immune Ontogeny

Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of granulocytic or monocytic cells that suppress innate as well as adaptive immune responses. In healthy adults, immature myeloid cells differentiate into macrophages, dendritic cells, and granulocytes in the bone marrow and MDSC are rarely detected in peripheral blood. However, in certain pathologies, in particular malignancies and chronic infection, differentiation of these cells is altered resulting in accumulation of circulating suppressive myeloid cells. MDSC express suppressive factors such as arginase-1, reactive oxygen species, and inducible nitric oxide synthase, which have the ability to inhibit T cell proliferation and cytoxicity, induce the expansion of regulatory T cells, and block natural killer cell activation. It is increasingly recognized that MDSC alter the immune response to several cancers, and perhaps chronic viral infections, in clinically important ways. In this review, we outline the potential contribution of MDSC to the generation of feto-maternal tolerance and to the ineffective immune responses to many infections and vaccines observed in early post-natal life. Granulocytic MDSC are present in large numbers in pregnant women and in cord blood, and wane rapidly during infancy. Furthermore, cord blood MDSC suppress in vitro T cell and NK responses, suggesting that they may play a significant role in human immune ontogeny. However, there are currently no data that demonstrate in vivo effects of MDSC on feto-maternal tolerance or immune ontogeny. Studies are ongoing to evaluate the functional importance of MDSC, including their effects on control of infection and response to vaccination in infancy. Importantly, several pharmacologic interventions have the potential to reverse MDSC function. Understanding the role of MDSC in infant ontogeny and their mechanisms of action could lead to interventions that reduce mortality due to early-life infections.

Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

“…In humans, MDSCs are HLA-DR Ϫ or HLA-DR low and CD11b ϩ , CD33 ϩ , or CD15 ϩ (19). MDSCs are immunosuppressive and have been shown to suppress the functions of NK cells, T cells, and B cells (20,21). The suppressive activity of MDSCs appears to be inversely related to the expression of the programmed death 1 protein (PD-1), as MDSCs from PD-1 Ϫ/Ϫ mice are more immunosuppressive than those from wild-type mice (20).…”

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

“…MDSCs are a heterogeneous subsets of immature and progenitor myeloid cells that are characterized by their strong immunosuppressive ability, such as suppress NK and NKT cells, CD4 + and CD8 + T cells cytotoxic reactivity, modulate macrophages to an immunosuppressive M2 phenotype and induce the generation of regulatory T cells and regulatory DCs [6,27]. MDSCs have been extensively investigated and its clinical relevance was proposed in various malignancies in last two decades.…”

“…The hallmark of MDSCs is their ability to suppress both innate and adaptive immune responses [6]. Suppressive factors expressed by MDSCs, such as arginase-1, reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS) and program death ligand 1(PDL-1), play pivotal roles in inhibition of T cell, B cell and natural killer cell (NK) mediated immune responses, and in induction of tolerogenic Tregs and regulatory dendritic cells (DCs) [7].…”

Future Perspectives of Tyrosine Kinase Inhibitors Discontinuation in Chronic Myeloid Leukemia

“…Myeloidderived suppressor cells (MDSC) have been extensively studied in recent years owing to their role in suppressing immune responses of many pathological conditions, including cancer [16]. MDSCs could suppress T-cells and natural killer cells, as well as antigen-presenting cells, abrogating the beneficial immune response [17]. For MDSCs could be amplified by cancer cells, they might connect the CML-LSC and T cells.…”