Embelin impairs the accumulation and activation of MDSCs in colitis-associated tumorigenesis

Myeloid-derived suppressor cells (MDSCs) are a major component of the immunosuppressive tumor microenvironment and has been recognized as a contributing factor for inflammation-related cancers. We previously showed that embelin has potent anti-inflammatory and anti-tumor effects in a colitis-associated cancer (CAC) model. Here, by using this model, we assessed the effect of embelin on the accumulation and suppressive function of MDSCs. We have demonstrated that embelin substantially reduced accumulation of MDSCs in the peripheral lymphoid organ and tumor tissue of CAC-bearing mice. Embelin impaired immunosuppressive activity of MDSCs by reducing the generation of reactive oxygen species (ROS) and arginase 1 level, leading to restored T cell responses. In tumor milieu, embelin increased the infiltration of CD8⁺ T cells, NK cells and mature dendritic cells whilst depleted the regulatory T cells. Moreover, embelin could directly interfere with the generation and function of MDSCs in vitro. These effects of embelin on MDSCs were mediated largely via limiting C/EBPβ and STAT3 signaling. Our findings support the hypothesis that embelin may be a promising pharmacologic agent in regulating MDSC-mediated immune tolerance in colorectal cancer.