The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highl...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 76; no. 23; pp. 6816 - 6827
Main Authors:	Wen, Shu Wen, Sceneay, Jaclyn, Lima, Luize Goncalves, Wong, Christina S F, Becker, Melanie, Krumeich, Sophie, Lobb, Richard J, Castillo, Vanessa, Wong, Ke Ni, Ellis, Sarah, Parker, Belinda S, Möller, Andreas
Format:	Journal Article
Language:	English
Published:	United States 01-12-2016
Subjects:	Animals Breast Neoplasms - immunology Breast Neoplasms - pathology Cell Proliferation Exosomes - metabolism Female Humans Immunosuppression - methods Mice Mice, Inbred BALB C Mice, Inbred C57BL
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Summary:	Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45 bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.can-16-0868