The Yin and Yang of Myeloid Derived Suppressor Cells

Abstract

In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their “Yin and Yang” nature in a more comprehensive and coherent manner.

Hypofractionated Irradiation Suppressed the Off-Target Mouse Hepatocarcinoma Growth by Inhibiting Myeloid-Derived Suppressor Cell-Mediated Immune Suppression

“…However, high-dose ablative IR reduced the level of MDSCs (22). We found the same results in two HCC tumorbearing mouse models: (1) the higher the IR dose/fraction, the bigger the off-target effect (Figure 2); (2) the bigger the tumor, the higher the blood MDSCs (both G-MDSCs and M-MDSCs) (C-E) The bone marrow cells were harvested from C57BL/6 or Institute of Cancer Research (ICR) mice and co-cultured with CM from Hepa1-6 or H22 cells irradiated with different single doses (0, 2.5, 4, 6, or 8 Gy). Three days later, the differentiation of the bone marrow cells into MDSCs or their proliferated was monitored by CD11b/Gr1 staining or 5,6-carboxyfluorescein diacetate (CFSE) assay.…”

“…Myeloid derived suppressor cells (MDSCs), a group of highheterogeneity immune-negative regulating cells, have two subgroups: granulocytic MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) with their own functions (1). In pathological conditions (such as an infection and an autoimmune disease), overproduced inflammation molecules and overstimulated proliferation, and differentiation of immune cells could be restrained by MDSCs to keep the reaction under control and to balance immune response and host's homeostasis (2).…”

Circulating CD14+HLA‐DR−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

“…M-MDSCs produce high amounts of NO, Arginase I (Arg-1), and immunosuppressive cytokines, such as IL-10, which suppress both antigen-specific and nonspecific T-cell responses. Mo-MDSCs are more potent suppressors than PMN-MDSCs because of NO, which has a longer half-life than ROS and reacts at greater distances [12]. A study revealed that Mo-MDSC (CD14 + HLA-DR −/low ) fractions were elevated in psoriasis patient peripheral blood mononuclear cells (PBMCs) compared to healthy controls, and, importantly, regulatory T cells induced by psoriasis Mo-MDSCs displayed decreased suppressive functionality [13].…”

Altered crosstalk of estradiol and progesterone with Myeloid‐derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal‐fetal tolerance

“…1 Considerable evidence has now been accumulated from the work previously reported by our group and others that a group of heterogeneous, immature cells of myeloid origin referred as myeloid-derived suppressor cells (MDSCs) is master regulator of many immune and nonimmune functions during early pregnancy. 3 These cells display both Yin and Yang behavior.…”

“…These cells display both Yin and Yang behavior. 3 Role of MDSCs was first shown in pathological settings such as cancer, sepsis, trauma where differentiation of these cells gets blocked and this blockage of differentiation leads to compromised immunity and favors progression of diseased state. 4,5 Interestingly, our group because of immunosuppressive nature of MDSCs is interested to explore the YANG side of these cells particularly its role in maternal-fetal tolerance.…”