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Science. 2016 Apr 8;352(6282):242-6. doi: 10.1126/science.aaf1328. Epub 2016 Mar 17.

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

Author information

1
Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA.
2
Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA. Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Neurology, Massachusetts General Hospital Research Institute, Harvard Medical School, Charlestown, MA 02129, USA.
4
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
5
Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
6
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Research Institute, Harvard Medical School, Charlestown, MA 02129, USA.
7
Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA. mpittet@mgh.harvard.edu.

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.

PMID:
26989197
PMCID:
PMC4960636
DOI:
10.1126/science.aaf1328
[Indexed for MEDLINE]
Free PMC Article

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