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Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

2014; Springer Nature; Volume: 24; Issue: 10 Linguagem: Inglês

10.1038/cr.2014.121

1748-7838

Yuan Yin, Xing Fu Cai, Xi Chen, Hongwei Liang, Yujing Zhang, Jing Li, Zuoyun Wang, Xiulan Chen, Wen Zhang, Seiji Yokoyama, Cheng Wang, Liang Li, Limin Li, Dongxia Hou, Lei Dong, Tao Xu, Takachika Hiroi, Fuquan Yang, Hongbin Ji, Junfeng Zhang, Ke Zen, Chen‐Yu Zhang,

Immunotherapy and Immune Responses

An increased population of CD4+CD25highFoxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles (MVs). In targeted mouse peripheral CD4+ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog (PTEN) and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides (ASOs) into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion.