Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges

Abstract

Immune cells such as T cells, macrophages, dendritic cells, and other immunoregulatory cells undergo metabolic reprogramming in cancer and inflammation-derived microenvironment to meet specific physiologic and functional demands. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are characterized by immunosuppressive activity, which plays a key role in host immune homeostasis. In this review, we have discussed the core metabolic pathways, including glycolysis, lipid and fatty acid biosynthesis, and amino acid metabolism in the MDSCs under various pathologic situations. Metabolic reprogramming is a determinant of the phenotype and functions of MDSCs, and is therefore a novel therapeutic possibility in various diseases.

Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good

“…Altogether, these data indicate that MDSCs from COVID-19 patients exert their suppressive activity using different mechanisms, which possibly depend on the MDSC subsets involved. MDSCs establish different metabolic pathways in different microenvironments, determining different mechanisms of suppression ( 85 ). Whether the diverse degrees of severity of COVID-19 could influence the suppressive functions of MDSCs needs further investigation.…”

Myeloid‐derived suppressor cells: Are they involved in gestational diabetes mellitus?

“…Arginine catabolism through Arg1 or NOS2 plays an important role in determining the immunologic fate of MDSCs. Arg1‐mediated arginine deprivation and NOS2‐mediated release of peroxynitrite can induce T cell apoptosis and inhibition of T cell function 116 . Ma et al.…”

“…Competitive uptake of amino acids in the extracellular environment is considered a mechanism for the expansion and immunosuppressive activity of MDSCs in cancers 115 . MDSCs with high metabolic rates can compete with cytotoxic T lymphocytes (CTLs) and NK cells for essential amino acids including arginine, tryptophan, and cysteine, that restrict their survival and induce apoptosis 116 . Arginine catabolism through Arg1 or NOS2 plays an important role in determining the immunologic fate of MDSCs.…”

“…Arg1-mediated arginine deprivation and NOS2-mediated release of peroxynitrite can induce T cell apoptosis and inhibition of T cell function. 116 Ma et al found that the levels of 26 amino acids including alanine, glycine, leucine and aspartic acid were significantly upregulated in MDSCs in the sepsis mice. 117 These findings underline the linkage between GDM-associated metabolic disruptions and MDSC fate.…”

“…115 MDSCs with high metabolic rates can compete with cytotoxic T lymphocytes (CTLs) and NK cells for essential amino acids including arginine, tryptophan, and cysteine, that restrict their survival and induce apoptosis. 116 Arginine catabolism through Arg1 or NOS2 plays an important role in determining the immunologic fate of MDSCs. Arg1-mediated arginine deprivation and NOS2-mediated release of peroxynitrite can induce T cell apoptosis and inhibition of T cell function.…”