[HTML][HTML] Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets

L Muller, M Mitsuhashi, P Simms, WE Gooding… - Scientific reports, 2016 - nature.com
L Muller, M Mitsuhashi, P Simms, WE Gooding, TL Whiteside
Scientific reports, 2016nature.com
Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in
the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were
evaluated. CD4+ Tconv, CD8+ T or CD4+ CD39+ Treg were isolated from normal donors'
peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of
cultured dendritic cells (DEX). Expression levels of 24–27 immune response-related genes
in these T cells were quantified by qRT-PCR. In activated T cells, TEX and DEX up-regulated …
Abstract
Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4+ Tconv, CD8+ T or CD4+ CD39+ Treg were isolated from normal donors’ peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of cultured dendritic cells (DEX). Expression levels of 24–27 immune response-related genes in these T cells were quantified by qRT-PCR. In activated T cells, TEX and DEX up-regulated mRNA expression levels of multiple genes. Multifactorial data analysis of ΔCt values identified T cell activation and the immune cell type, but not exosome source, as factors regulating gene expression by exosomes. Treg were more sensitive to TEX-mediated effects than other T cell subsets. In Treg, TEX-mediated down-regulation of genes regulating the adenosine pathway translated into high expression of CD39 and increased adenosine production. TEX also induced up-regulation of inhibitory genes in CD4+ Tconv, which translated into a loss of CD69 on their surface and a functional decline. Exosomes are not internalized by T cells, but signals they carry and deliver to cell surface receptors modulate gene expression and functions of human T lymphocytes.
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