Publication Date:
2016-03-19
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pucci, Ferdinando -- Garris, Christopher -- Lai, Charles P -- Newton, Andita -- Pfirschke, Christina -- Engblom, Camilla -- Alvarez, David -- Sprachman, Melissa -- Evavold, Charles -- Magnuson, Angela -- von Andrian, Ulrich H -- Glatz, Katharina -- Breakefield, Xandra O -- Mempel, Thorsten R -- Weissleder, Ralph -- Pittet, Mikael J -- 1R01CA164448/CA/NCI NIH HHS/ -- 1R33CA202064/CA/NCI NIH HHS/ -- F31-CA196035/CA/NCI NIH HHS/ -- P01-CA069246/CA/NCI NIH HHS/ -- P50-CA86355/CA/NCI NIH HHS/ -- R01 AI097052/AI/NIAID NIH HHS/ -- R01-AI084880/AI/NIAID NIH HHS/ -- R01EB010011/EB/NIBIB NIH HHS/ -- R21-CA190344/CA/NCI NIH HHS/ -- T32CA79443/CA/NCI NIH HHS/ -- U19 CA179563/CA/NCI NIH HHS/ -- U54-CA126515/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):242-6. doi: 10.1126/science.aaf1328. Epub 2016 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA. ; 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. ; Department of Neurology, Massachusetts General Hospital Research Institute, Harvard Medical School, Charlestown, MA 02129, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland. ; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Research Institute, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA. mpittet@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989197" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/*immunology/ultrastructure
;
Cell Communication
;
Extracellular Vesicles/*immunology
;
Humans
;
*Immune Tolerance
;
Lymph Nodes/immunology
;
Lymphatic Vessels/immunology
;
Macrophages/chemistry/*immunology
;
Melanoma/*immunology/pathology
;
Melanoma, Experimental/immunology/pathology
;
Mice
;
Mice, Inbred C57BL
;
Sialic Acid Binding Ig-like Lectin 1/analysis/immunology
;
Skin Neoplasms/*immunology/pathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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