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.
Highlights
INTRODUCTIONMacrophages, dendritic cells, polymorphonuclear granulocytic cells and others are continuously generated from hematopoietic stem cells through multi-step differentiation processes
Myeloid cells encompassing monocytes, macrophages, dendritic cells, polymorphonuclear granulocytic cells and others are continuously generated from hematopoietic stem cells through multi-step differentiation processes
The majority of correlative data between myeloid-derived suppressor cells” (MDSCs) and clinical outcomes pertains to cancer, where the presence of cells with phenotypes of one type or another have been associated with patient survival in many different tumors including melanoma [38], breast [39], lung [40], and others
Summary
Macrophages, dendritic cells, polymorphonuclear granulocytic cells and others are continuously generated from hematopoietic stem cells through multi-step differentiation processes. MDSCs have been most intensively studied in the context of cancer [3] They are a very heterogeneous group of mononuclear and polymorphonuclear myeloid cells, normally present at very low numbers in healthy individuals, but may accumulate under disease conditions [4]—or potentially during natural aging [5, 6] or with psychological stress [7]. In this article, we will attempt to briefly review [1] how best to identify MDSCs in humans; [2] what are their suppressive mechanisms and how to target them pharmacologically; [3] if their levels of MDSCs informative for clinical outcomes; and [4] whether MDSCs are only important in pathology or whether they represent physiological regulatory mechanisms for the feedback control of immunity In this latter section, relying mostly on studies in mouse models which can be experimentally manipulated, a basis is established for translating animal data to areas less well-documented than cancer in humans. Because the role of MDSCs in cancer has been subject to considerable recent scrutiny [reviewed in [11, 12]], we will only very briefly cover this issue and focus more on the importance of MDSCs in other conditions
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