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.2016-02-082016-02-0820150036-8075http://hdl.handle.net/11693/26419The 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.EnglishAnatomyBloodCancerCells and cell componentsDisease treatmentImmune systemRespiratory diseaseRodentTumorAnimal cellAnimal experimentAnimal modelArticleCancer controlCell interactionCell specificityCell transferControlled studyFemaleIn vivo studyLung metastasisMicrovasculatureMonocyteMouseNatural killer cellNonhumanPriority journalTumor cellTumor invasionAnimalExperimental neoplasmGeneticsImmunologyImmunosurveillanceImmunotherapyLung NeoplasmsMetastasisMonocyteMutant mouse strainProceduresSecondaryMusNr4a1 protein, mouseNuclear receptor Nur77AnimalsImmunologic SurveillanceImmunotherapyKiller Cells, NaturalLung NeoplasmsMiceMice, Mutant StrainsMonocytesNeoplasm InvasivenessNeoplasm MetastasisNeoplasms, ExperimentalNuclear Receptor Subfamily 4, Group A, Member 1Article10.1126/science.aac9407