Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

Michael P. Plebanek, Nicholas L. Angeloni, Elena Vinokour, Jia Li, Anna Henkin, Dalia Martinez-Marin, Stephanie Filleur, Reshma Bhowmick, Jack Henkin, Stephen D. Miller, Igal Ifergan, Yesung Lee, Iman Osman, C. Shad Thaxton, Olga V. Volpert*

*Corresponding author for this work

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6Clow patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. These events require the induction of the Nr4a1 transcription factor and are dependent on pigment epithelium-derived factor (PEDF) on the outer surface of exosomes. Importantly, exosomes isolated from patients with non-metastatic primary melanomas have a similar ability to suppress lung metastasis. This study thus demonstrates that pre-metastatic tumors produce exosomes, which elicit a broad range of PMo-reliant innate immune responses via trigger(s) of immune surveillance, causing cancer cell clearance at the pre-metastatic niche.

Original languageEnglish (US)
Article number1319
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Plebanek, M. P., Angeloni, N. L., Vinokour, E., Li, J., Henkin, A., Martinez-Marin, D., Filleur, S., Bhowmick, R., Henkin, J., Miller, S. D., Ifergan, I., Lee, Y., Osman, I., Thaxton, C. S., & Volpert, O. V. (2017). Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nature communications, 8(1), [1319]. https://doi.org/10.1038/s41467-017-01433-3