4.8 Article

Patrolling monocytes control tumor metastasis to the lung

期刊

SCIENCE
卷 350, 期 6263, 页码 985-990

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac9407

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资金

  1. NIH [R01 HL118765, R01 CA202987, NIH F32 HL117533-02]
  2. American Heart Association [3POST16990029, 125SDG12070005]
  3. La Jolla Institute for Allergy and Immunology Board of Directors Fellowship
  4. CNRS
  5. INSERM
  6. SIgN (A*STAR)

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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.

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