title: Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets.
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.
authors: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.|Department of Otolaryngology and Head &Neck Surgery, University Hospital in Basel, CH 4031 Basel, Switzerland.
authors: Laurent
authors: L
authors: Muller
authors: Hitachi Chemical Research Center, Inc., Irvine, CA 92617, USA.
authors: Masato
authors: M
authors: Mitsuhashi
authors: FACS Core Facility, Loyola University School of Medicine, Maywood, Il 60153, USA.
authors: Patricia
authors: P
authors: Simms
authors: Division of Biostatistics, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors: William E
authors: WE
authors: Gooding
authors: 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.
authors: Theresa L
authors: TL
authors: Whiteside
mesh_terms: D000241:Adenosine / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099192:CD69 Antigens
chemical_list: D000241:Adenosine; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001081:Apyrase; D017077:Culture Media, Conditioned; D037181:Lectins, C-Type; D012333:RNA, Messenger; D000099192:CD69 Antigens; C067869:CD39 antigen