Cianciaruso, Beltraminelli, and Duval et al. examined the proteome of TAM-derived extracellular vesicles (TAM-EVs) from MC38 colorectal tumors and found enrichment of proteins related to immune responses and enzymes involved in the metabolism and biosynthesis of lipids that play a role in inflammation signaling. While TAMs showed a pro-tumoral, M2-like phenotype, TAM-EVs enhanced T cell proliferation and activation ex vivo and displayed an antitumoral M1-like gene signature, which correlated with improved survival in human cancers. Similar results were observed in other tumor models.
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.
Author Info: (1) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic addre
Author Info: (1) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: chiara.cianciaruso@epfl.ch. (2) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (3) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (4) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (5) Proteomics Core Facility, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (6) Flow Cytometry Core Facility, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (7) Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland. (8) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (9) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. (10) Roche Innovation Center Munich, Roche Pharma Research and Early Development, 82377 Penzberg, Germany. (11) Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland. (12) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: michele.depalma@epfl.ch.
