Macrophage Polarization by Tumor-induced MDSCs Assay

Abstract

Myeloid derived suppressor cells (MDSCs) are a subset of granulocytes (immature myeloid cells) that exploit a variety of mechanism to modulate the innate and adaptive immune system. MDSCs are present normally in the body, but their numbers increase during inflammation and in cancer, promoting an immunosuppressive microenvironment. In addition to MDSCs, macrophages also play an important role during cancer development. There are two subsets of tumor associated macrophages (TAMs): M1 and M2. M1 are “anti-tumor” macrophages that are activated by interferon gamma (IFN-γ) and/or Lipopolysaccharide (LPS) and secrete high amount of interleukin 12 (IL-12) thereby inducing a Th1 anti-tumor immune response. M2 or “pro-tumorigenic” macrophages are activated by interleukin 4 (IL-4) and interleukin 10 (IL-10) and secrete large amounts of IL-10, which promotes tumor progression (Gabrilovich et al., 2012).Interaction between MDSCs and macrophages in the tumor microenvironment was shown to enhance immune suppression mediated by these subsets. MDSCs influence TAMs by producing IL-10 that, in turn, induces a down-regulation of IL-12 and polarizes M1 into M2 macrophages. In our study, we use the following protocol to evaluate the ability of tumor induced MDSCs to polarize LPS activated M1 into M2 macrophages (Vences-Catalan et al., 2015). This protocol was adapted from a previous study (Sinha et al., 2007).