Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity

Abstract

Since the realization that immature myeloid cells are powerful modulators of the immune response, many studies on “myeloid-derived suppressor cells” (MDSCs) have documented their ability to promote tumor progression in melanoma and other cancers. Whether MDSCs are induced solely pathologically in tumorigenesis, or whether they also represent physiological immune control mechanisms, is not well-understood, but is particularly important in the light of ongoing attempts to block their activities in order to enhance anti-tumor immunity. Here, we briefly review studies which explore (1) how best to identify MDSCs in the context of cancer and how this compares to other conditions in humans; (2) what the suppressive mechanisms of MDSCs are and how to target them pharmacologically; (3) whether levels of MDSCs with various phenotypes are informative for clinical outcome not only in cancer but also other diseases, and (4) whether MDSCs are only found under pathological conditions or whether they also represent a physiological regulatory mechanism for the feedback control of immunity. Studies unequivocally document that MDSCs strongly influence cancer outcomes, but are less informative regarding their relevance to infection, autoimmunity, transplantation and aging, especially in humans. So far, the results of clinical interventions to reverse their negative effects in cancer have been disappointing; thus, developing differential approaches to modulate MSDCs in cancer and other diseases without unduly comprising any normal physiological function requires further exploration.

A Cellular Study of Inflammatory Responses in Women with Polycystic Ovary Syndrome as: “An In vitro Model of Anti Breast Tumor Response”A Case Control Study

“…Chronic in ammation and obesity can cause deviation of cell differentiation to myeloid derived suppressor cells (MDSCs) (43,44). Low-grade in ammatory environments in women with PCOS and the presence of obesity as well in these patients may stimulate peripheral differentiation of MDSCs that these cells may suppress e cient tumor response to breast cancer (45).…”

miRNAs as Key Players in the Management of Cutaneous Melanoma

“…M1 polarization of macrophages is regulated by miR-29a, and miR-21 is overexpressed in the blood of melanoma patients, targeting COL4A2, SPARC, and TIMP3 [73].Through the interaction between the NKG2D receptor and its ligand NKG2DL, Natural Killer (NK) cells are able to kill tumor cells but this ability is impaired by miR-34a/c and miR-449a/miR-449c [74]. In addition, Myeloid-Derived Suppressor Cells (MDSCs), whose role in cancer is still under evaluation, while its immune suppressive role is well-known [75], could be directly/indirectly regulated by miRNAs. miR-155 is able to induce MDSCs recruitment in TME [76], inhibiting SOCS1.…”

Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)

“…Gr-1 is comprised of Ly6C and Ly6G that represent monocytic and granulocytic MDSCs, respectively (71). Due to the lack of homolog for Gr-1, human MDSCs are generally called mononuclear/monocytic (M-MDSC) and polymorphonuclear/granuclocytic (PMN-MDSC) cells (72). M-MDSCs are defined as CD11b + CD14 + HLA-DR −/lo CD15 − and PMN-MDSCs as CD11b + CD14 − CD15 + or CD11b + CD14 − CD66b + (71).…”

“…Lin − HLA-DR − CD33 + are early stage MDSCs that can be found from human, but their equivalent in mice is not known yet (71). Physiologically, MDSCs are advantageous in semi-allogenic situations, such as pregnancy or transplantation, but they are better known for their disadvantageous immunosuppressive functions in chronic pathologies, for example, in chronic infections or cancer (72,73) (Figure 2). MDSCs can regulate both innate and adaptive immune responses, e.g., by modulating macrophages, inhibiting NK or T cell responses or by inducing regulatory T cells (2, 5, [74][75][76][77][78][79].…”