Abstract
Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells in the tumor microenvironment, contributing to tumor immunological escapes. Many studies have demonstrated that multiple factors could induce myeloid precursor cells into myeloid-derived suppressor cells, not dendritic cells. In our study, we found that tumor supernatants could induce the generation of myeloid-derived suppressor cells by disturbing the development of dendritic cells. Twist and miR-34a may regulate the effect of tumor cells inducing myeloid-derived suppressor cells via TGF-β and/or IL-10.
Highlights
The tumor microenvironment is well known to be immunosuppressive [1,2,3,4]
IL-12, IL-6, TNF, IL-10, transforming growth factor-β (TGF-β) were assayed by ELISA and NO were assayed by Griess
We proved that miR-34a mimics and Twist siRNA could suppress the secretion of IL-10 and TGF-β
Summary
The tumor microenvironment is well known to be immunosuppressive [1,2,3,4]. Tumor-derived factors such as TGF-β, VEGF, IL-10, and PGE2 and other factors such as gangliosides and lactate have been verified to be able to regulate differentiation and function of dendritic cells (DC) and T cells [5,6,7]. It has been well established that the tumor microenvironment could drive imDC (immature dendritic cells) to differentiate into CD11bhighIalow regulatory DC via TGF-β and PGE2, and that regulatory DC suppress T cells response [8]. Myeloid precursor cells may differentiate into DC, macrophages, granulocytes and mast cells depending on the microenvironmental conditions. They might stay in non-differentiated mixed form, which include myeloid-derived suppressor cells (MDSC) [9,10]. MDSC and DC share the same myeloid precursor cell, and play very different roles in the immune response. We tried to test whether tumor supernatant could induce myeloid precursor cells into MDSC, not DC, and elucidated the roles of Twist and miR-34a in the process. We hope that this research may provide a new understanding of the mechanism of tumor immune escape
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