The biodistribution and immune suppressive effects of breast cancer-derived exosomes

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. and Moller, Andreas (2016) The biodistribution and immune suppressive effects of breast cancer-derived exosomes. Cancer Research, 76 23: 6816-6827. doi:10.1158/0008-5472.CAN-16-0868

Author 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.
Moller, Andreas
Title The biodistribution and immune suppressive effects of breast cancer-derived exosomes
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
Publication date 2016-12-01
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-16-0868
Open Access Status Not yet assessed
Volume 76
Issue 23
Start page 6816
End page 6827
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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