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Regulatory T cell (Treg) expansion-mediated immune tolerance is generally associated with tumorigenesis.However, the mechanism underlying the expansion of Treg by cancer cells remains incompletely understood.Here we report that microRNAs secreted by cancer cells induce CD4+CD25+ Tregs.Cancer cells increase plasma miR-214 level in cancer patients and tumor-implanted mice.Microvesicles (MVs)-containing miR-214 secreted from cancer cells entered into CD4+ T cells, reduced the expression of phosphatase and tensin homolog (PTEN), leading to the polarization of CD4+ T cells into Tregs in vitro and in vivo.Furthermore, Tregs, whose numbers were increased due to circulating miR-214, facilitated the growth of implanted tumors in mice.In contrast, MV-delivered anti-miR-214 antisense oligonucleotides blocked the Treg induction by miR-214 secreted by implanted cancer ceils and decreased tumor growth.Our results provide the first evidence that cancer cell can actively secret miRNA to promote Treg expansion and therefore to facilitate cancer cell immune escape.