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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.

Author information

1
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
2
Department of Otolaryngology and Head &Neck Surgery, University Hospital in Basel, CH 4031 Basel, Switzerland.
3
Hitachi Chemical Research Center, Inc., Irvine, CA 92617, USA.
4
FACS Core Facility, Loyola University School of Medicine, Maywood, Il 60153, USA.
5
Division of Biostatistics, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
6
Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

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.

PMID:
26842680
PMCID:
PMC4740743
DOI:
10.1038/srep20254
[Indexed for MEDLINE]
Free PMC Article

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