Pucci, FerdinandoGarris, ChristopherLai, CharlesNewton, AnditaPfirschke, ChristinaEngblom, CamillaAlvarez, DavidSprachman, MelissaEvavold, CharlesMagnuson, Angelavon Andrian, Ulrich H.Glatz, KatharinaBreakefield, XandraMempel, ThorstenWeissleder, RalphPittet, Mikael2019-09-212016Pucci, F., C. Garris, C. P. Lai, A. Newton, C. Pfirschke, C. Engblom, D. Alvarez, et al. 2016. “SCS Macrophages Suppress Melanoma by Restricting Tumor-Derived Vesicle-B Cell Interactions.” Science 352 (6282): 242–46. https://doi.org/10.1126/science.aaf1328.0036-80751095-9203http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384248Tumor-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 tEVdissemination 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.en-USJournal Article2019-09-2110.1126/science.aaf1328