Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model.

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells and . EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4 and CD8 T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5 μg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs . EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including , , , , , , , and . Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.