SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions

Ferdinando Pucci, Christopher Garris, Charles P. Lai, Andita Newton, Christina Pfirschke, Camilla Engblom, David Alvarez, Melissa Sprachman, Charles Evavold, Angela Magnuson, Ulrich H. Von Andrian, Katharina Glatz, Xandra O. Breakefield, Thorsten R. Mempel, Ralph Weissleder, Mikael J. Pittet

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101 Scopus citations

Abstract

Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169+ macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169+ macrophage layer physically blocks tEV dissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169+ macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity.

Original languageEnglish (US)
Pages (from-to)242-246
Number of pages5
JournalScience
Volume352
Issue number6282
DOIs
StatePublished - Apr 8 2016
Externally publishedYes

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Cite this

Pucci, F., Garris, C., Lai, C. P., Newton, A., Pfirschke, C., Engblom, C., Alvarez, D., Sprachman, M., Evavold, C., Magnuson, A., Von Andrian, U. H., Glatz, K., Breakefield, X. O., Mempel, T. R., Weissleder, R., & Pittet, M. J. (2016). SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science, 352(6282), 242-246. https://doi.org/10.1126/science.aaf1328