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      • Department of Molecular Biology and Genetics
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      Patrolling monocytes control tumor metastasis to the lung

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      Author(s)
      Hanna, R. N.
      Cekic, C.
      Sag, D.
      Tacke, R.
      Thomas, G. D.
      Nowyhed, H.
      Herrley, E.
      Rasquinha, N.
      McArdle, S.
      Wu, R.
      Peluso, E.
      Metzger, D.
      Ichinose, H.
      Shaked, I.
      Chodaczek, G.
      Biswas, S. K.
      Hedrick, C. C.
      Date
      2015
      Source Title
      Science
      Print ISSN
      0036-8075
      Publisher
      American Association for the Advancement of Science
      Volume
      350
      Issue
      6263
      Pages
      985 - 990
      Language
      English
      Type
      Article
      Item Usage Stats
      139
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      108
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      Abstract
      The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.
      Keywords
      Anatomy
      Blood
      Cancer
      Cells and cell components
      Disease treatment
      Immune system
      Respiratory disease
      Rodent
      Tumor
      Animal cell
      Animal experiment
      Animal model
      Article
      Cancer control
      Cell interaction
      Cell specificity
      Cell transfer
      Controlled study
      Female
      In vivo study
      Lung metastasis
      Microvasculature
      Monocyte
      Mouse
      Natural killer cell
      Nonhuman
      Priority journal
      Tumor cell
      Tumor invasion
      Animal
      Experimental neoplasm
      Genetics
      Immunology
      Immunosurveillance
      Immunotherapy
      Lung Neoplasms
      Metastasis
      Monocyte
      Mutant mouse strain
      Procedures
      Secondary
      Mus
      Nr4a1 protein, mouse
      Nuclear receptor Nur77
      Animals
      Immunologic Surveillance
      Immunotherapy
      Killer Cells, Natural
      Lung Neoplasms
      Mice
      Mice, Mutant Strains
      Monocytes
      Neoplasm Invasiveness
      Neoplasm Metastasis
      Neoplasms, Experimental
      Nuclear Receptor Subfamily 4, Group A, Member 1
      Permalink
      http://hdl.handle.net/11693/26419
      Published Version (Please cite this version)
      http://dx.doi.org/10.1126/science.aac9407
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      • Department of Molecular Biology and Genetics 468
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