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

A Möller1,2

  1. Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. School of Medicine, University of Queensland, Brisbane, Australia

Small membranous vesicles secreted from tumour cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumour microenvironment. Using optical imaging we determined that exogenously administrated (intravenous) fluorescently-labelled exosomes, derived from highly metastatic murine breast cancer cells, distribute predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the lung, exosomes are taken up by approximately 14% of CD45+ immune cells. Subsequent characterisation of infiltrating immune cells in breast cancer exosome-conditioned lung revealed an immunosuppressed environment in non-tumour bearing mice, with an accumulation of myeloid-derived suppressor cells, yet decreased T-cell and Natural Killer cell frequency. This immune suppressive effect led to increased metastatic burden in a mammary experimental metastasis model. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation as well as inhibited NK cell cytotoxicity, and hence likely suppress the anti-cancer immune response. Together, our findings provide a novel and important insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to anti-cancer immune suppression and the promotion of metastasis.