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Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Authors Ferguson Bennit HR, Gonda A, Oppegard LJ, Chi DP, Khan S, Wall NR

Received 21 December 2016

Accepted for publication 27 January 2017

Published 28 February 2017 Volume 2017:7 Pages 9—23


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor David Dingli

Heather R Ferguson Bennit,1,2 Amber Gonda,1,3 Laura J Oppegard,2 David P Chi,2 Salma Khan,1,2 Nathan R Wall1,2

Center for Health Disparities & Molecular Medicine, 2Division of Biochemistry, Department of Basic Sciences, 3Department of Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA

Abstract: Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake.

Keywords: exosome, non-Hodgkin’s lymphoma, B cell

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