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Science. 2015 Nov 20;350(6263):985-90. doi: 10.1126/science.aac9407. Epub 2015 Oct 22.

Patrolling monocytes control tumor metastasis to the lung.

Author information

  • 1Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. rhanna@lji.org hedrick@lji.org.
  • 2Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
  • 3Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey.
  • 4Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • 5Microscopy Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • 6Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, Illkirch, France.
  • 7Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
  • 8Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.

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.

Copyright © 2015, American Association for the Advancement of Science.

PMID:
26494174
[PubMed - indexed for MEDLINE]
PMCID:
PMC4869713
Free PMC Article
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