Tumor-secreted MiR-214 Induces Regulatory T Cells: a Major Link Between Immune Evasion and Tumor Growth

Overview

Journal Cell Res

Specialty Cell Biology

Date 2014 Sep 17

PMID 25223704

Citations 156

Authors

Yuan Yin

Xing 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

Affiliations

Soon will be listed here.

Abstract

An increased population of CD4(+)CD25(high)Foxp3(+) 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.

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