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Sci Rep. 2016 Feb 4;6:20254. doi: 10.1038/srep20254.

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

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University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Department of Otolaryngology and Head &Neck Surgery, University Hospital in Basel, CH 4031 Basel, Switzerland.
Hitachi Chemical Research Center, Inc., Irvine, CA 92617, USA.
FACS Core Facility, Loyola University School of Medicine, Maywood, Il 60153, USA.
Division of Biostatistics, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.


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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