title: The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.
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. Cancer Res; 76(23); 6816-27. ©2016 AACR.
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Shu Wen
authors.initials: SW
authors.lastname: Wen
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Sceneay
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Luize Goncalves
authors.initials: LG
authors.lastname: Lima
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Christina S F
authors.initials: CS
authors.lastname: Wong
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Becker
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Sophie
authors.initials: S
authors.lastname: Krumeich
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lobb
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Castillo
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Ke Ni
authors.initials: KN
authors.lastname: Wong
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, and Sir Peter MacCallum Department of Histology, University of Melbourne, Parkville, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ellis
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Parker
authors.affiliation: Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. andreas.moller@qimrberghofer.edu.au.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Möller
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL