TY - JOUR
T1 - Patrolling monocytes control tumor metastasis to the lung
AU - Hanna, Richard N.
AU - Cekic, Caglar
AU - Sag, Duygu
AU - Tacke, Robert
AU - Thomas, Graham D.
AU - Nowyhed, Heba
AU - Herrley, Erica
AU - Rasquinha, Nicole
AU - McArdle, Sara
AU - Wu, Runpei
AU - Peluso, Esther
AU - Metzger, Daniel
AU - Ichinose, Hiroshi
AU - Shaked, Iftach
AU - Chodaczek, Grzegorz
AU - Biswas, Subhra K.
AU - Hedrick, Catherine C.
PY - 2015/11/20
Y1 - 2015/11/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947754755&partnerID=8YFLogxK
U2 - 10.1126/science.aac9407
DO - 10.1126/science.aac9407
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C2 - 26494174
AN - SCOPUS:84947754755
SN - 0036-8075
VL - 350
SP - 985
EP - 990
JO - Science
JF - Science
IS - 6263
ER -