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Melanoma-released exosomes directly activate the mitochondrial apoptotic pathway of CD4+ T cells through their microRNA cargo.

Abstract：

:Tumor-derived exosomes (TEX) play an important role in the escape of tumor cells from immune surveillance. However, the details of the mechanism are not fully understood. In this study, the apoptosis of CD4+ T cells increased during treatment with B16-derived exosomes in vitro and in vivo, resulting in accelerated growth of melanoma cells in mice. While the release of exosomes was blocked by disrupting the expression of Rab27a, tumor growth was clearly inhibited, and the percentage of T cells in the tumor environment increased. At the same time, Western blot showed that TEX could increase the activation of caspase-3, caspase-7 and caspase-9 but not caspase-8, down-regulating the anti-apoptotic proteins, including BCL-2, MCL-1 and BCL-xL in CD4+ T cells, and indicating that the TEX activates the mitochondrial apoptotic pathway of CD4+ T cells. These reductions were probably associated with the release of microRNAs, such as miR-690, from TEX to T cells. Our present study reveals for the first time that melanoma-released exosomes may directly activate the mitochondrial apoptotic pathway of CD4+ T cells through their microRNA cargo.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Zhou J,Yang Y,Wang W,Zhang Y,Chen Z,Hao C,Zhang J

doi

10.1016/j.yexcr.2018.08.030

subject

Has Abstract

pub_date

2018-10-15 00:00:00

pages

364-371

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(18)30788-2

journal_volume

371

pub_type

杂志文章

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