Patrolling monocytes control tumor metastasis to the lung.
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.
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. rhanna@lji.org hedrick@lji.org.
Richard N
RN
Hanna
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Caglar
C
Cekic
Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey.
Duygu
D
Sag
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Robert
R
Tacke
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Graham D
GD
Thomas
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Heba
H
Nowyhed
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Erica
E
Herrley
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Nicole
N
Rasquinha
Microscopy Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Sara
S
McArdle
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Runpei
R
Wu
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Esther
E
Peluso
Department 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.
Daniel
D
Metzger
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Hiroshi
H
Ichinose
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Iftach
I
Shaked
Microscopy Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Grzegorz
G
Chodaczek
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Subhra K
SK
Biswas
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. rhanna@lji.org hedrick@lji.org.
Catherine C
CC
Hedrick
D000818:Animals; D007157:Immunologic Surveillance / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary* / Q000628:therapy; D051379:Mice; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology / Q000556:secondary; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics
C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1