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 microvasculatur...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2015-11, Vol.350 (6263), p.985-990 |
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| creator | Hanna, Richard N. Cekic, Caglar Sag, Duygu Tacke, Robert Thomas, Graham D. Nowyhed, Heba Herrley, Erica Rasquinha, Nicole McArdle, Sara Wu, Runpei Peluso, Esther Metzger, Daniel Ichinose, Hiroshi Shaked, Iftach Chodaczek, Grzegorz Biswas, Subhra K. Hedrick, Catherine C. |
| description | 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. |
| doi_str_mv | 10.1126/science.aac9407 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aac9407</identifier><identifier>PMID: 26494174</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Activation ; Animals ; Blocking ; Cancer ; Immune system ; Immune systems ; Immunologic Surveillance - immunology ; Immunotherapy ; Immunotherapy - methods ; Killer Cells, Natural - immunology ; Lung Neoplasms - immunology ; Lung Neoplasms - secondary ; Lung Neoplasms - therapy ; Lungs ; Metastasis ; Mice ; Mice, Mutant Strains ; Monocytes - immunology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Experimental - immunology ; Neoplasms, Experimental - secondary ; Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics ; Recruitment ; Tumors</subject><ispartof>Science (American Association for the Advancement of Science), 2015-11, Vol.350 (6263), p.985-990</ispartof><rights>Copyright © 2015 American Association for the Advancement of Science</rights><rights>Copyright © 2015, American Association for the Advancement of Science.</rights><rights>Copyright © 2015, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-586dfcd32ff9046dfafddb2c02ac7298aac72b738323509108f9e994044b8aa63</citedby><cites>FETCH-LOGICAL-c586t-586dfcd32ff9046dfafddb2c02ac7298aac72b738323509108f9e994044b8aa63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24740849$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24740849$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,777,781,800,882,2871,2872,27905,27906,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26494174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanna, Richard N.</creatorcontrib><creatorcontrib>Cekic, Caglar</creatorcontrib><creatorcontrib>Sag, Duygu</creatorcontrib><creatorcontrib>Tacke, Robert</creatorcontrib><creatorcontrib>Thomas, Graham D.</creatorcontrib><creatorcontrib>Nowyhed, Heba</creatorcontrib><creatorcontrib>Herrley, Erica</creatorcontrib><creatorcontrib>Rasquinha, Nicole</creatorcontrib><creatorcontrib>McArdle, Sara</creatorcontrib><creatorcontrib>Wu, Runpei</creatorcontrib><creatorcontrib>Peluso, Esther</creatorcontrib><creatorcontrib>Metzger, Daniel</creatorcontrib><creatorcontrib>Ichinose, Hiroshi</creatorcontrib><creatorcontrib>Shaked, Iftach</creatorcontrib><creatorcontrib>Chodaczek, Grzegorz</creatorcontrib><creatorcontrib>Biswas, Subhra K.</creatorcontrib><creatorcontrib>Hedrick, Catherine C.</creatorcontrib><title>Patrolling monocytes control tumor metastasis to the lung</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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. 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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.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>26494174</pmid><doi>10.1126/science.aac9407</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Animals Blocking Cancer Immune system Immune systems Immunologic Surveillance - immunology Immunotherapy Immunotherapy - methods Killer Cells, Natural - immunology Lung Neoplasms - immunology Lung Neoplasms - secondary Lung Neoplasms - therapy Lungs Metastasis Mice Mice, Mutant Strains Monocytes - immunology Neoplasm Invasiveness Neoplasm Metastasis Neoplasms, Experimental - immunology Neoplasms, Experimental - secondary Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics Recruitment Tumors |
| title | Patrolling monocytes control tumor metastasis to the lung |
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