Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression

结肠直肠癌细胞衍生的细胞外囊泡通过转化生长因子-β1介导的抑制诱导 T 细胞表型改变为肿瘤生长支持细胞

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作者:Nami Yamada, Yuki Kuranaga, Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi, Yukihiro Akao

Abstract

Emerging studies on tumor cell-derived extracellular vesicles (EVs) have shown the biological significance in tumor development and microenvironment through reprogramming immune cells around cancer cells. In this study, we used colorectal cancer cells as EVs donor, and T cells as recipients to examine whether EVs impair the T cell function. As a result, we found that colorectal cancer cell-derived EVs (CRC-EVs) were enriched with TGF-β1. Interestingly, CRC-EVs induced phenotypic alteration of the T cells to Treg-like cells through activating TGF-β/Smad signaling and inactivating SAPK signaling. Furthermore, the CRC-EVs-induced-Treg-like cells had a remarkable tumor-growth promoting activity in vitro and in vivo. These results suggest that colorectal cancer cells utilize EVs to tame immune cells for their prosperity.

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