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Ava Rhule Smith, Joseph M Reynolds, Editorial: The contribution of myeloid-derived suppression to inflammatory disease, Journal of Leukocyte Biology, Volume 96, Issue 3, Sep 2014, Pages 361–364, https://doi.org/10.1189/jlb.3CE0414-205R
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Both innate and adaptive immune mechanisms exist to restrain inflammatory T lymphocyte responses and protect against excessive host damage. Aberrant activation of regulatory mechanisms, however, can lead to strong immunosuppression that is detrimental in infectious diseases and cancer. In the adaptive immune response, Tregs represent one such regulatory mechanism with well-defined markers and roles in restricting inflammation [1]. The characteristics exhibited by immunosuppressive cells of the innate immune response are not as clear. It has been known for a number of years that a heterogeneous population of CD11b+Gr1+ cells, collectively known as MDSCs, is associated with the repression of anti-tumor T cells. Likewise, MDSC-like cells are also expanded under inflammatory conditions, which may represent a relatively unexplored regulatory mechanism with the potential to influence the course and outcome of the immune response.
In mice, MDSCs can be generally classified as G-MDSCs (CD11b+Ly6G+) or M-MDSCs (CD11b+Ly6C+), with a variety of additional markers and suppressor mechanisms further subdividing the population (reviewed in ref. [2]). Both types of MDSC subsets are up-regulated in various cancers, where they have been shown to inhibit deleteriously T cell-dependent tumor immunity [2]. Although human and mouse MDSCs can use many different suppressive mechanisms, the predominant means are arginase 1 and iNOS enzymatic activity, which are important for L-arginine starvation and the inhibition of T cell signaling [2, 3]. Additionally, MDSCs have been implicated in inhibiting the activation of anti-tumorigenic cells, such as CD8+ T cells and NK cells, while still using various cell-contact and soluble mechanisms to promote reciprocally antigen-specific activation and expansion of inducible Tregs [4]. MDSCs were also recently found to suppress further anti-tumor responses through the production of peroxynitrite, which interferes with the binding of tumor-specific antigens to MHC class I and results in evasion from CD8+ T cell recognition [5].
