Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with recently escalating incidence and generally dismal outcomes (1,2). By far, surgical resection is still considered as the first option for HCC cure (3). However, postoperative survival remains unsatisfactory because of high recurrence and metastasis rates due to the high invasiveness potential of HCC cells (4-6). Therefore, a better understanding of HCC cell spread may provide novel insights into HCC management in the future. The transforming growth factor-β1 (TGFβ1)-induced TGFβ signaling pathway has been reported to play a vital role in HCC progression and spread (7). Active TGFβ1 could trigger epithelial–mesenchymal transition (EMT) in a Smad2/3-dependent manner, greatly promoting the invasiveness of tumor cells (8-10). Previous studies reported that regulatory T (Treg) cells were a critical resource of TGFβ1, and Treg-derived TGFβ1 could also promote tumor invasion (11,12). However, whether infiltrating Treg was an important origin of TGFβ1 in HCC, and its role in promoting HCC progression, remained elusive