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Cell Rep. 2019 Jun 4;27(10):3062-3080.e11. doi: 10.1016/j.celrep.2019.05.008.

Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles.

Author information

1
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: chiara.cianciaruso@epfl.ch.
2
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
3
Proteomics Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
4
Flow Cytometry Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
5
Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland.
6
Roche Innovation Center Munich, Roche Pharma Research and Early Development, 82377 Penzberg, Germany.
7
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: michele.depalma@epfl.ch.

Abstract

Extracellular vesicles (EVs), including exosomes, modulate multiple aspects of cancer biology. Tumor-associated macrophages (TAMs) secrete EVs, but their molecular features and functions are poorly characterized. Here, we report methodology for the enrichment, quantification, and proteomic and lipidomic analysis of EVs released from mouse TAMs (TAM-EVs). Compared to source TAMs, TAM-EVs present molecular profiles associated with a Th1/M1 polarization signature, enhanced inflammation and immune response, and a more favorable patient prognosis. Accordingly, enriched TAM-EV preparations promote T cell proliferation and activation ex vivo. TAM-EVs also contain bioactive lipids and biosynthetic enzymes, which may alter pro-inflammatory signaling in the cancer cells. Thus, whereas TAMs are largely immunosuppressive, their EVs may have the potential to stimulate, rather than limit, anti-tumor immunity.

KEYWORDS:

T cell response; exosome; extracellular vesicle; inflammation; lipid metabolism; lipidomics; proteomics; tumor microenvironment; tumor-associated macrophage

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