期刊
CELL RESEARCH
卷 24, 期 10, 页码 1164-1180出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2014.121
关键词
secreted microRNA; regulatory T cell; PTEN; microvesicle; immune evasion; tumor
类别
资金
- National Basic Research Program of China (973 Program) [2014CB542300]
- National Natural Science Foundation of China [81101330, 31271378, 81250044]
- Natural Science Foundation of Jiangsu Province [BK2011013, BK2012014]
- Research Special Fund for Public Welfare Industry of Health [201302018]
- Ministry of Education of China [NCET-12-0261]
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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