Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles
Chiara Cianciaruso,
Tim Beltraminelli,
Florent Duval,
Sina Nassiri,
Romain Hamelin,
André Mozes,
Hector Gallart-Ayala,
Gerardo Ceada Torres,
Bruno Torchia,
Carola H. Ries,
Julijana Ivanisevic,
Michele De Palma
Affiliations
Chiara Cianciaruso
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland; Corresponding author
Tim Beltraminelli
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Florent Duval
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Sina Nassiri
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Romain Hamelin
Proteomics Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
André Mozes
Flow Cytometry Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Hector Gallart-Ayala
Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland
Gerardo Ceada Torres
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Bruno Torchia
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Carola H. Ries
Roche Innovation Center Munich, Roche Pharma Research and Early Development, 82377 Penzberg, Germany
Julijana Ivanisevic
Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland
Michele De Palma
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland; Corresponding author
Summary: 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. : Cianciaruso et al. develop methods for the analysis of extracellular vesicles secreted by macrophages in mouse tumors (TAM-EVs). Proteomic and lipidomic profiling indicates that TAM-EVs carry modulators of inflammation and lipid metabolism that could influence the properties of the tumor immune microenvironment. Keywords: extracellular vesicle, exosome, tumor microenvironment, tumor-associated macrophage, proteomics, lipidomics, lipid metabolism, inflammation, T cell response